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Demonstration of the Th1 to Th2 cytokine shift during the course of HIV‐1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry

Klein, Stefan A.1,2; Dobmeyer, Jürgen M.1; Dobmeyer, Thomas S.1; Pape, Martine1; Ottmann, Oliver G.1; Helm, Eilke B.1; Hoelzer, Dieter1; Rossol, Rita1

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Author Information

1Medical Clinic III, Johann Wolfgang Goethe University, Frankfurt, Germany.

2Requests for reprints to: Dr Stefan A. Klein, Universitätsklinik Frankfurt, Medizinische Klinik III, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.

Sponsorship: This work was supported by the Bundesministerium für Forschung und Technologie grant 01KI9406

Date of receipt: 20 August 1996; revised: 18 March 1997; accepted: 16 April 1997.

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Objective: To characterize changes of Th1/Th2 cytokine production by peripheral blood mononuclear cells (PBMC) that occur during the course of HIV infection by cytoplasmic cytokine staining on single cell level.

Design and methods: Mitogen-stimulated PBMC from 16 healthy donors, 18 HIV-1-infected individuals without AIDS and 14 patients with AIDS were stained intracellularly with fluorescein-labelled MAb against interleukin (IL)-2, IL-4, IL-10 and interferon (IFN)-γ. Additionally, co-staining of CD4+ T-cell, CD8+ T-cell, natural killer (NK) cell, B-cell and monocytic markers was performed. Fluorescence staining was analysed by three-colour flow-cytometry.

Results: A reduced percentage of IL-2 and IFN-γ (Th1 type)-producing cells among CD4+ T cells from HIV-1-infected individuals could be demonstrated. There was a continuous decrease of IFN-γ-producing CD4+ T cells in the course of HIV infection and a dramatic reduction of IL-2-expressing cells among CD4+ T cells in patients with AIDS. In contrast to Th1 cytokines, the frequency of Th2 cytokine expressing cells among CD4+ T cells increased in HIV-infected individuals. The maximum frequency of IL-4-expressing cells among CD4+ T cells was seen in HIV-infected individuals without AIDS, whereas the rate of IL-10-producing cells was highest in patients with AIDS. In HIV-infected individuals no significant proportion of Th0 cells expressing both Th1 and Th2 cytokines was detectable. In CD8+ T cells the percentage of IL-2 was expressing cells decreased continuously accompanied by a strong increase of the frequency of IFN-γ-producing cells.

Conclusion: The decreased percentage of cells expressing IL-2 and IFN-γ in conjunction with an increased proportion of IL-4- and IL-10-producing cells among the CD4+ T cells in HIV-1-infected individuals demonstrate a Th1 to Th2 cytokine shift in the course of HIV infection on a single cell level. There was no evidence of a Th1 to Th0 cytokine shift. In addition to the loss of CD4+ T cells in HIV infection, the qualitative changes of Th1/Th2 cytokine expression may serve as a marker for progressive failure of cell-mediated immunity.

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Apart from the loss of CD4+ T cells, defects in T-cell immune function such as a reduced expression of Th1 cytokines can be detected in HIV-infected individuals [1–5]. Moreover, the regular occurrence of a polyclonal B-cell activation and hypergammaglobulinaemia suggests that the Th2-type cytokine expression may be increased. However, changes in the pattern of Th1- and Th2-type cytokine expression in the course of HIV infection are discussed controversially. Whereas Clerici and others [6–12] observed a Th1 to Th2 cytokine shift, several authors have proposed either a Th1 to Th0 shift [13–17] or contradict a change of Th1/Th2 cytokine pattern [18].

A dichotomy between Th1 and Th2 has been identified in murine CD4+ T cells [19]. Analysis of T-cell clones in humans have shown an analogous, although not identical, cytokine synthesis heterogeneity [20–23]. Th1 and Th2 CD4+ T cells are characterized exclusively by differences in cytokine expression: Th1 cells produce interleukin (IL)-2, IL-12 and interferon (IFN)-γ, whereas Th2 cells express IL-4, IL-5, IL-6, IL-10 and IL-13 [20]. Moreover, it has been shown that the Th1/Th2 cytokine heterogeneity is not only restricted to CD4+ T cells [20]. Cell types such as CD8+ T cells or natural killer (NK) cells contribute to the Th1/Th2 cytokine heterogeneity as well. Thus, the terms Th1-type or Th2-type cytokine or cell are used to characterize the cytokine profile of the different cell types.

Due to the different methods used for assessing cytokine expression [e.g., enzyme-linked immunosor-bent assay (ELISA), reverse transcriptase (RT)-polymerase chain reaction (PCR) or T-cell-cloning and differences between the examined T-cell populations obtained from peripheral blood or lymph nodes, the results of Th1/Th2-cytokine expression in HIV-infected individuals are contradictory. None of the conventional methods for measuring cytokine expression used in earlier reports facilitates characterization of cytokine production of T cells directly. To circumvent this problem, we employed the method of cytoplasmic cytokine staining to determine whether the suggested Th1 to Th2 cytokine-shift indeed occurs in course of HIV infection. Using this method we were able to characterize and distinguish cells which are solely defined by their cytokine production such as Th1- and Th2-type T cells. In addition, it is possible to detect cytokine production of cells on single cell level without previous cell sorting.

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Material and methods

Study population

Peripheral blood was obtained with informed consent from 16 healthy adult donors, from 18 HIV-1-infected donors classified Centers for Disease Control and Prevention (CDC) 1993 criteria stage A1, A2, B1, and B2 and from 14 HIV-1-infected individuals in CDC stage C3. Patients suffering from malignancies (except Kaposi's sarcoma) and individuals receiving chemotherapy were excluded.

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Cell preparation and culture

Peripheral blood mononuclear cells (PBMC) were isolated by Ficoll-Histopaque (Sigma, Deisenhofen, Germany) density gradient centrifugation. Cells were adjusted to a concentration of 1 × 106 cells/ml in RPMI 1640 medium (Gibco, Karlsruhe, Germany) containing heat inactivated fetal calf serum (Gibco), 100 U/ml penicillin, 100 μg/ml streptomycin and 1 mM glutamine (Biochrom, Berlin, Germany).

PBMC were cultured using a modification of the conditions reported by Jung et al. [24]: cells were stimulated with 5 ng/ml PMA (phorbol 12-myristate 13-acetate) in combination with 0.75 μg/ml ionomycin (Sigma) in round bottom tissue culture tubes (Greiner, Nürtingen, Germany). Monensine (Sigma) was added in a concentration of 3 μM to prevent cytokine release. Cultures without the addition of monensine and without exogenous stimuli were included as controls. The optimal duration of incubation for induction of each cytokine had been determined previously in time kinetic experiments. The detection of IFN-γ, IL-2 and IL-4 was optimal after a culture time of 5 h in contrast to 10 h for IL-10.

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Fixation, permeabilization and cytokine-staining

After incubation the cells were stained according to methods described elsewhere, with slight modifications [24–26]. The cells were washed twice in Hank's balanced salt solution (HBSS) and fixed with 4% paraformaldehyde in HBSS at 4°C for 10 minutes. After two further washing steps in HBSS, the cells were resuspended at a concentration of 2 × 105/tube in permeabilization buffer (HBSS containing 0.1% saponin, 0.01 M Hepes buffer and 5% type AB serum) and incubated for 5 min. The cells were then pelleted and resuspended in the remaining buffer after decantation. Anti-cytokine-specific monoclonal antibodies (MAb) were added in concentrations ranging from 0.1 to 1 μg/ml for 20 min at 20°C followed by two further washing steps in permeabilization buffer.

The following cytokine-specific MAb were used: unlabelled anti-IFN-γ mouse IgG2a (Genzyme, Boston, Massachusetts, USA), anti-IFN-γ-fluorescein isothiocyanate (FITC) (Hölzel Diagnostika, Cologne, Germany), anti IL-2-biotin mouse IgG2a, clone N7.48A (Hölzel), anti IL-4-biotin mouse IgG1, clone 8F12 (Hölzel) and anti-IL10-phycoerythrin (PE) rat IgG1 clone JES3-9D7 (PharMingen, San Diego, California, USA). Isotype controls were unlabelled or labelled with FITC, PE, or biotin (Dianova, Hamburg, Germany).

To ensure specificity of MAb staining, the binding of anti-cytokine-specific antibodies was blocked with a molar excess of the corresponding recombinant cytokine.

Cells stained with unlabelled or biotinilated MAb were pelleted again and incubated with a second FITC or PE-labelled antibody (Dianova) or a streptavidin-PE-conjugate (Serotec, Wiesbaden, Germany) for 20 min followed by two further washing steps in permeabilization buffer. After indirect antibody-staining the cells were washed twice with permeabilization buffer.

As a last step, surface phenotyping was performed with FITC, PE or peridine chlorophyll a protein (PerCP)-labelled MAb against CD3, CD4, CD8, CD56, CD20 and CD14 (Becton Dickinson, Heidelberg, Germany).

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Flow cytometry

Fluorescence staining was analysed by three-colour flow cytometry on a FACScan flow cytometer using Lysys II software (Becton Dickinson). Routinely, 1 × 104 PBMC were analysed. For evaluation of cytokine expression in less frequent cell types such as CD4+ T cells in HIV-infected individuals, at least 2000 cells were counted. Cell populations < 1% (< 20 events) were not regarded as significant. For analysis of double cytokine staining the acquisition of CD4+ or CD8+ T cells was performed using a life gate. The cutoff point, at which a cytokine-specific signal was considered to be positive was determined using unstimulated cells and cells stained with isotype-specific antibodies. The average amount of cytokine production per cell was evaluated by measuring the cytokine-specific intensity of fluorescence. Due to the high day-to-day and even inter-experimental variability of fluorescence intensity the absolute values of fluorescence intensity cannot be used for quantification of cytokine production. To facilitate a comparison of the cytokine expression in various cell types from different donors, a ratio of the mean intensity of fluorescence staining per cell expressing a certain cytokine and of the fluorescence intensity at the cut-off point determined for this cytokine was calculated. Statistical analysis was performed using the Wilcoxon-Mann-Whitney test.

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PBMC from 16 healthy donors, 18 HIV-1-infected individuals without AIDS and 14 patients with AIDS were stimulated in vitro for cytokine production. After a 5 h or 10 h incubation permeabilized cells were stained intracellularly with cytokine-specific MAb against IL-2, IL-4, IL-10 and IFN-γ in combination with MAb-staining of surface markers for CD4+ T cells, CD8+ T cells, NK cells, B cells and monocytes in order to determine the frequency of Th1- or Th2-type cytokine expression in these cell types.

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Th1-type cytokines

Analysis of the Th1-type cytokines IL-2 and IFN-γ in CD4+ T cells revealed that the percentage of cells expressing these cytokines decreased with disease progression. The percentage of CD4+ T cells producing IFN-γ decreased continuously from 19.6 ± 3.0 in healthy donors to 14.0 ± 1.8 in HIV-1-infected individuals classified CDC stages A1, B1, A2 and B2 and to 10.6 ± 1.9 in patients with AIDS (CDC C3). A dramatic reduction in the proportion of IL-2-expressing cells starting from 35.2 ± 5.5% among CD4+ T cells from HIV-1-infected individuals classified CDC A1, B1, A2 and B2 to 9.6 ± 1.5% in patients with AIDS was detectable (Table 1, Fig. 1). In contrast to the CD4+ T cells, the percentage of IFN-γ-expressing cells was higher among CD8+ T cells obtained from patients classified CDC C3 (51.4 ± 7.6) as compared to healthy donors (23.2 ± 4.2, Table 1, Fig. 1).

Table 1
Table 1
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Fig. 1
Fig. 1
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Th2-type cytokines

The frequency of CD4+ T cells from healthy donors expressing IL-4 or IL-10 is significantly (P < 0.01) lower than that of those expressing Th1-type cytokines: Only 3.0 ± 0.5% of CD4+ T cells were positive for IL-4; IL-10 was almost undetectable. The percentage of both IL-4 and IL-10-producing cells among CD4+ T cells from HIV-1-infected individuals was increased in comparison to healthy donors. The proportion of CD4+ T cells expressing IL-4 was significantly (P < 0.05) higher in cells from HIV-1-infected individuals without AIDS (6.2 ± 1.3%). Whereas the frequency of IL-4 expression was reduced among CD4+ T cells from patients with AIDS, the percentage of IL-10-producing cells increased significantly (P < 0.01) during the course of infection, reaching 5.3 ± 1.4 among CD4+ T cells obtained from patients with AIDS (Table 2, Fig. 1). Both IL-4 and IL-10 were almost undetectable in CD8+ T cells from healthy donors and expressed weakly in a minor fraction of cells from HIV-infected individuals (< 2.5%).

Table 2
Table 2
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Cytokine expression in non-T-cells

In order to evaluate the frequency of non-T-cells expressing Th1 or Th2 cytokines B cells, NK cells and monocytes were also investigated regarding their cytokine production. Following PMA/ionomycin or LPS stimulation no IL-2, IL-4, IL-10 or IFN-γ production could be detected in either monocytes (CD14+ cells) or B cells (CD20+ cells; data not shown).

Whereas IL-4 was undetectable in NK cells from any donor group, 5–24% of NK cells (CD8+/CD56+) obtained from healthy donors as well as from HIV-infected individuals expressed the Th1-type cytokines IL-2 or IFN-γ. The expression of these cytokines did not correlate with the presence or the stage of HIV infection (data not shown).

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Double staining of Th1- and Th2-cytokines

In order to determine whether cells expressing Th-2 cytokines are Th-2 or Th-0 type T cells, cells were stained simultaneously with MAb against Th1- and Th2-cytokines. Double-staining of IFN-γ and IL-4 revealed that nearly all CD4+ T cells (98.6 ± 2.3%) from HIV-infected individuals expressing IL-4 do not produce IFN-γ (Fig. 2). Moreover, the majority (64.3 ± 5.4) of IL-4 expressing CD4+ T cells from HIV-1-infected individuals did not co-express IL-2. The frequency of IL-4 expressing cells among CD8+ T cells was lower than among CD4+ T cells. IL-4 and IFN-γ were not co-expressed in CD8+ T cells. Concerning the double staining of IL-2 and IL-4, fewer than 40% of the CD8+ T cells that expressed IL-4 produced IL-2.

Fig. 2
Fig. 2
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Quantification of cytokine production

In order to compare the average cytokine expression per CD4+ T cell obtained from the three donor-groups, a ratio of the mean fluorescence intensity per cytokine expressing cell and the fluorescence intensity at the cut-off point was calculated. The intensity of Th1-cytokine staining per CD4+ T cell was reduced significantly in patients with AIDS. Concerning IL-4, there was a peak of cytokine expression per cell in HIV-infected individuals without AIDS compared with both the patients with AIDS and the healthy controls. The level of IL-10 expression per cell was highest in CD4+ T cells from patients with AIDS (Table 3).

Table 3
Table 3
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The depletion of CD4+ T cells during the course of HIV infection is accompanied by a progressive loss of cell-mediated immunity [2,3]. This loss of T-cell function occurs with a reduced production of IL-2 and IFN-γ by PBMC [6,7,9,12]. Observations such as polyclonal B-cell activation resulting in hypergammaglobulinaemia or increased IgE-serum-levels led to the suggestion of an increased Th2-type cytokine expression resulting in a Th1 to Th2 shift during the course of HIV infection [6,7]. Moreover, dysregulation of Th1/Th2 cytokine expression had been proposed as a mechanism for T cell loss via induction of apoptosis in HIV infection [27].

Our data showing a reduced frequency of IL-2 or IFN-γ-producing cells among CD4+ T cells and an increased percentage of IL-4 or IL-10 positive cells among CD4+ T cells confirm for the first time on a single cell level the proposed Th1 to Th2 shift of cytokine production in CD4+ T cells of HIV-1-infected individuals.

As it is shown in Table 1 the percentage of IL-2-expressing cells among CD4+ T cells from HIV-infected individuals classified CDC A1, B1, A2 and B2 was reduced significantly in comparison with patients with AIDS (CDC C3). Thus, the loss of IL-2-expressing CD4+ T cells may be a critical step towards the development of AIDS.

The percentage of CD4+ T cells capable of expression of Th-2 cytokines is very low in uninfected donors (IL-4, 2.9%; IL-10, < 1%). As it has been shown earlier, a significant increase of IL-4 expression is associated with early stages of the disease [8,28]. More than twice as many CD4+ T cells were positive for IL-4 in HIV-infected donors classified CDC A1, B1, A2 and B2 compared with healthy donors. Moreover, the average IL-4 production per CD4+ T cell was enhanced significantly in HIV-infected individuals indicating a strong Th2-type response. Surprisingly IL-4 expression peaked in early stages of HIV infection and decreased again with the development of AIDS. Although these results are consistent with earlier results [6,8] the cause and significance of this phenomenon still have to be identified. Whereas IL-4 expression had its maximum in early stages of the disease, IL-10 was expressed particularly in patients with AIDS: both, the percentage of CD4+ T cells producing IL-10 and the average IL-10 expression per cell peaked in individuals suffering from AIDS.

The increased Th-2-type cytokine expression in CD4+ T cells from HIV-infected individuals could be demonstrated not to be a Th0-like response since we were able to show by double staining of IFN-γ versus IL-4 and IL-2 versus IL-4 that the Th2 cytokine IL-4 is rarely co-expressed with Th-2 cytokines. Thus, we suggest that there is a Th1 to Th2 shift of cytokine expression in HIV-infected individuals. Unfortunately we could not generate similar data for IL-10 because IL-10 has its maximal expression after a 10 h incubation whereas an optimal staining for IL-2 and IFN-γ is achieved after 5 h.

As demonstrated in Table 1 and Fig. 1, an increase of the percentage of IFN-γ-expressing cells among CD8+ T cells was observed during the course of HIV infection. These results confirm similar earlier reported data [18,29]. The increased IFN-γ expression by CD8+ T cells may reflect an enhanced activation of cytotoxic T cells in course of HIV infection. This gives support to the theory of an increasing population of anti-HIV-specific CD8+ T cells [30,31], or an enhanced activation of CD8+ T cells in HIV infection.

Although the frequency of CD8+T cells expressing the Th1-type cytokine IFN-γ is increased in HIV-1-infected patients the total amount of IFN-γ production is not enhanced as it has been shown earlier [32,33]. Thus, the enhanced IFN-γ expression in CD8+ T cells does not contradict the suggested Th1 to Th2 shift.

However, examination of Th1/Th2-cytokine expression in non-T-cell lymphocytes demonstrated no significant cytokine production in B cells. The percentage of Th1-type cytokine expressing cells among NK cells obtained from HIV-infected individuals was neither increased nor decreased compared with healthy donors: between 5% and 24% of NK cells obtained from healthy donors and HIV-infected individuals expressed IL-2 or IFN-γ. Th2-type cytokines were not detectable in NK cells from all donor groups. Thus, neither B cells nor NK cells appear to contribute to a change of Th1/Th2 cytokine expression during the course of HIV infection.

Monocytes could be important producers of Th1 (IL-12) or Th2 (IL-10) cytokines. In this study we could not characterize monocytic expression of these cytokines by cytoplasmic cytokine staining. Thus, stimulation, culture and intracellular cytokine staining of monocytes have to be optimized to characterize the contribution of this cell type to changes of Th1/Th2 cytokine expression in HIV infection.

One may criticize the fact that the low frequency of Th2-type cytokine-expressing cells among CD4+ T cells, which represent also only a minority of cells in HIV infection, could hardly contribute significantly to the change of cytokine pattern: the Th1/Th2 cytokine heterogeneity could be demonstrated for CD4+ T cells and for CD4 negative lymphocytes [20]. As described above, even monocytes are producers of Th1- or Th2-type cytokines. However, a Th1 to Th2 shift could be demonstrated on a single cell level only in CD4+ T cells in early (IL-4) and in late (IL-10) stages of HIV infection. Therefore the Th1 to Th2 shift in HIV infection, which was already demonstrated in culture supernatants or by RT-PCR [6–12] should be due to the Th1 to Th2 shift in the CD4+ T-cell compartment. Moreover, for the induction of a cell mediated immunity by Th1-type or a humoral immune response by Th2-type cytokines CD4+ T cells are playing a central role. Therefore, even in HIV-infected individuals with a low count of CD4+ T cells the cytokine expression of this cell type should be pivotal for the Th1/Th2-cytokine pattern.

For stimulation of PBMC, a combination of PMA and ionomycin was used. This maximal activation gives the opportunity to define the capability of lymphocytes to produce cytokines. Other more physiological stimuli such as anti-CD3-MAb (OKT3) or anti-CD28 MAb did not result in a cell activation sufficient for cytoplasmic cytokine staining. After such a stimulation even IL-2 or IFN-γ were expressed in fewer than 5% of CD4+ T cells from healthy donors. Th2-type cytokines were almost undetectable in cells cultured for 4–12 h under these suboptimal stimulation conditions. Only after several restimulations with OKT3 and a culture time of 4–7 days were more than 20% of CD4+ T cells positive for IL-2 or IFN-γ (data not shown). Data obtained after such a long in-vitro culture time can be extremely biased in relation to the culture conditions and are therefore hardly reliable or valid to characterize or to represent any in vivo situation. Therefore we used a maximal stimulation in a short term culture as the best indicator for the in vivo capacity of cells to express Th1/Th2-cytokines.

In addition to the characterization of cells by their cytokine production, the method of cytoplasmic cytokine staining permits quantification of cytokine production per cell. Due to the inhibition of cytokine release by monensine, the intensity of cytokine staining per cell reflects the amount of cytokines produced during monensine incubation. Thus, we were able to compare the amount of cytokine production per cell between different donors by creating a ratio between the mean of the fluorescence intensity and the staining intensity at the threshold of cytokine expression. In contrast to the absolute value of fluorescence intensity this ratio is not influenced by instrument settings and measurement-to-measurement variability of fluorescence intensity. As it has been shown earlier by Jung et al., quantification of cytokine expression by the method of cytoplasmic cytokine staining is valid and reliable [25,34].

Thus, cytoplasmic cytokine staining gives the unique opportunity to quantify cytokine expression within surface-marker-defined single cells. It can be a tool to characterize cytokine expression and to clarify the role of cytokines for pathogenesis of AIDS. Moreover, the question of whether cytoplasmic cytokine staining can be used to monitor the immune function of HIV-infected individuals has still to be investigated. Particularly for monitoring of disease progression under antiretroviral therapy, cytoplasmic cytokine detection would certainly add important information concerning the quality of the T-cell function to a monitoring based only on quantitative parameters such as the count of CD4+ T cells and virus burden. Moreover, compared with alternative techniques to analyse cytokine expression (e.g. RT-PCR or ELISA) cytoplasmic cytokine detection is performed more easily and cheaply and it also provides additional information.

The data presented in this paper demonstrate a shift of Th1-type to Th2-type cytokine expression by CD4+ T cells in the course of HIV infection in the setting of a cross-sectional study. In order to definitively prove the Th1 to Th2 cytokine shift during the course of HIV infection a longitudinal study will be performed.

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Brain, 136(): 1048-1066.
Tubercle and Lung Disease
Examining a paradox in the pathogenesis of human pulmonary tuberculosis: immune activation and suppression/anergy
Vanham, G; Toossi, Z; Hirsch, CS; Wallis, RS; Schwander, SK; Rich, EA; Ellner, JJ
Tubercle and Lung Disease, 78(): 145-158.

Journal of Virology
Intestinal intraepithelial lymphocytes are primed for gamma interferon and MIP-1 beta expression and display antiviral cytotoxic activity despite severe CD4(+) T-cell depletion in primary simian immunodeficiency virus infection
Mattapallil, JJ; Smit-McBride, Z; McChesney, M; Dandekar, S
Journal of Virology, 72(8): 6421-6429.

Journal of Allergy and Clinical Immunology
Atopy, anergic status, and cytokine expression in HIV-infected subjects
Empson, M; Bishop, GA; Nightingale, B; Garsia, R
Journal of Allergy and Clinical Immunology, 103(5): 833-842.

Dna and Cell Biology
Modulation of ex vivo cytokine production by splenocytes using in vitro combined therapeutics in murine retroviral model
Kang, LC; Kerben, MJ; Ugen, KE; Specter, SC
Dna and Cell Biology, 18(7): 585-592.

Immunology and Cell Biology
Interactions of HIV-1 with antigen-presenting cells
Hewson, T; Lone, N; Moore, M; Howie, S
Immunology and Cell Biology, 77(4): 289-303.

Archives of Pediatrics & Adolescent Medicine
Prevalence of and risks for cervical human papillomavirus infection and squamous intraepithelial lesions in adolescent girls - Impact of infection with human immunodeficiency virus
Moscicki, AB; Ellenberg, JH; Vermund, SH; Holland, CA; Darragh, T; Crowley-Nowick, PA; Levin, L; Wilson, CM
Archives of Pediatrics & Adolescent Medicine, 154(2): 127-134.

Interleukin-10-secreting CD4 cells from aged patients with AIDS decrease in-vitro HIV replication and tumour necrosis factor alpha production
Andrade, RM; Lima, PG; Filho, RGS; Hygino, J; Milczanowski, SF; Andrade, AFB; Lauria, C; Brindeiro, R; Tanuri, A; Bento, CAM
AIDS, 21(): 1763-1770.

Nitric Oxide-Biology and Chemistry
Nitric oxide production in mouse and rat macrophages: A rapid and efficient assay for screening of drugs immunostimulatory effects in human cells
Kmonickova, E; Melkusova, P; Farghali, H; Holy, A; Zidek, Z
Nitric Oxide-Biology and Chemistry, 17(): 160-169.
Viral Immunology
Detection of IgE Antibody Specific to a Hepatitis C Virus-Derived Peptide Being Recognized by Cellular Immunity in Patients with HCV Infection
Gohara, S; Shichijo, S; Komatsu, N; Okuda, S; Yutani, S; Itoh, K
Viral Immunology, 21(3): 365-369.
Journal of Infectious Diseases
Cytokine profile induced by Cryptosporidium antigen in peripheral blood mononuclear cells from immunocompetent and immunosuppressed persons with cryptosporidiosis
Morales, MAG; La Rosa, G; Ludovisi, A; Onori, AM; Pozio, E
Journal of Infectious Diseases, 179(4): 967-973.

AIDS Research and Human Retroviruses
B7 cosignal potentiates apoptosis of uninfected CD4(+) T lymphocytic cell lines primed by HIV envelope proteins
Coito, C; Bomsel, M
AIDS Research and Human Retroviruses, 15(6): 509-521.

Journal of Virology
Activated memory CD4(+) T helper cells repopulate the intestine early following antiretroviral therapy of simian immunodeficiency virus-infected rhesus macaques but exhibit a decreased potential to produce interleukin-2
Mattapallil, JJ; Smit-McBride, Z; Dailey, P; Dandekar, S
Journal of Virology, 73(8): 6661-6669.

New Concepts in the Immunopathogenesis of CNS Infections
Macaque models of the neuropathogenesis of HIV infection
Buch, S; David, SA; Cheney, PD; Raghavan, R; Narayan, O
New Concepts in the Immunopathogenesis of CNS Infections, (): 249-267.

AIDS Research and Human Retroviruses
Frequency of cytokine-producing T cells in HIV-infected patients treated with stavudine, didanosine, and ritonavir
Levacher, M; Bouscarat, F; Landman, R; Chau, F; Damond, F; Gaudebout, C; Mathez, D; Leibowitch, J; Saimot, AG; Sinet, M
AIDS Research and Human Retroviruses, 16(): 1869-1875.

Journal of Steroid Biochemistry and Molecular Biology
Association between AIDS disease progression rates and the Fok-I polymorphism of the VDR gene in a cohort of HIV-1 seropositive patients
Nieto, G; Barber, Y; Rubio, MC; Rubio, M; Fibla, J
Journal of Steroid Biochemistry and Molecular Biology, 89-0(): 199-207.
Journal of Leukocyte Biology
Regulation of the tonsil cytokine milieu favors HIV susceptibility
Moutsopoulos, NM; Vazquez, N; Greenwell-Wild, T; Ecevit, I; Horn, J; Orenstein, J; Wahl, SM
Journal of Leukocyte Biology, 80(5): 1145-1155.
Journal of Venomous Animals and Toxins Including Tropical Diseases
Immune reconstitution in HIV-1 infected patients treated for two years with highly active antiretroviral therapy
Almeida, RAMB; Souza, LR; Calvi, SA; Ikoma, MRV; Silva, VA; Curi, PR; Meira, DA
Journal of Venomous Animals and Toxins Including Tropical Diseases, 12(1): 91-109.

Journal of Investigative Dermatology
Epidermal Barrier Dysfunction in Non-Atopic HIV: Evidence for an "Inside-to-Outside'' Pathogenesis
Gunathilake, R; Schmuth, M; Scharschmidt, TC; Gruber, R; Grabher, D; Leslie, KS; Maurer, TA; Mauro, TM; Elias, PM
Journal of Investigative Dermatology, 130(4): 1185-1188.
Journal of Immunology
Differential susceptibility to activation-induced apoptosis among peripheral Th1 subsets: Correlation with Bcl-2 expression and consequences for AIDS pathogenesis
Ledru, E; Lecoeur, H; Garcia, S; Debord, T; Gougeon, ML
Journal of Immunology, 160(7): 3194-3206.

Pflugers Archiv-European Journal of Physiology
Involvement of adenylate cyclase and p70(S6)-kinase activation in IL-10 up-regulation in human monocytes by gp41 envelope protein of human immunodeficiency virus type 1
Barcova, M; Speth, C; Kacani, L; Uberall, F; Stoiber, H; Dierich, MP
Pflugers Archiv-European Journal of Physiology, 437(4): 538-546.

The RING finger ubiquitin ligase RNF125/TRAC-1 down-modulates HIV-1 replication in primary human peripheral blood mononuclear cells
Shoji-Kawata, S; Zhong, Q; Kameoka, M; Iwabu, Y; Sapsutthipas, S; Luftig, RB; Ikuta, K
Virology, 368(1): 191-204.
Clinical Immunology and Immunopathology
Differential expression of bcl-2 and susceptibility to programmed cell death in lymphocytes of HIV-1-infected individuals
Dobmeyer, TS; Klein, SA; Dobmeyer, JM; Raffel, B; Findhammer, S; Hoelzer, D; Helm, EB; Rossol, R; Kabelitz, D
Clinical Immunology and Immunopathology, 87(3): 230-239.

International Journal of Clinical & Laboratory Research
Functional Fas-ligand expression on T cells from HIV-1-infected patients is unrelated to CD4(+) lymphopenia
Silvestris, F; Cafforio, P; Camarda, G; Tucci, M; Frassanito, MA; Dammacco, F
International Journal of Clinical & Laboratory Research, 28(4): 215-225.

Journal of Immunology
Opposite effects of IL-10 on the ability of dendritic cells and macrophages to replicate primary CXCR4-dependent HIV-1 strains
Ancuta, P; Bakri, Y; Chomont, N; Hocini, H; Gabuzda, D; Haeffner-Cavaillon, N
Journal of Immunology, 166(6): 4244-4253.

Journal of Infectious Diseases
Comparison of the frequency of interleukin (IL)-2-, interferon-gamma-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes
Sousa, AE; Chaves, AF; Loureiro, A; Victorino, RMM
Journal of Infectious Diseases, 184(5): 552-559.

Immunological Reviews
Role of human Fc epsilon RI+ cells in HIV-1 infection
Marone, G; Florio, G; Petraroli, A; Triggiani, M; de Paulis, A
Immunological Reviews, 179(): 128-138.

AIDS Research and Human Retroviruses
HIV type 1 vaccine-induced T cell memory and cytotoxic T lymphocyte responses in HIV type 1-uninfected volunteers
Gorse, GJ; Patel, GB; Belshe, RB
AIDS Research and Human Retroviruses, 17(): 1175-1189.

Relative preservation of natural killer cell cytotoxicity and number in healthy AIDS patients with low CD4 cell counts
Ironson, G; Balbin, E; Solomon, G; Fahey, J; Klimas, N; Schneiderman, N; Fletcher, MA
AIDS, 15(): 2065-2073.

Increased expression of the inflammatory chemokine CXC chemokine ligand 9/monokine induced by interferon-gamma in lymphoid tissues of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome
Reinhart, TA; Fallert, BA; Pfeifer, ME; Sanghavi, S; Capuano, S; Rajakumar, P; Murphey-Corb, M; Day, R; Fuller, CL; Schaefer, TM
Blood, 99(9): 3119-3128.

Clinical and Experimental Immunology
Combined cyclosporin-A/prednisone therapy of patients with active uveitis suppresses IFN-gamma production and the function of dendritic cells
Frassanito, MA; Dammacco, R; Fusaro, T; Cusmai, A; Guerriero, S; Sborgia, C
Clinical and Experimental Immunology, 133(2): 233-239.

Immunological Investigations
Effects of the homeopathic preparation engystol on interferon-gamma production by human T-lymphocytes
Enbergs, H
Immunological Investigations, 35(1): 19-27.
Journal of Neuroimmunology
A vitamin A deficient diet enhances proinflammatory cytokine, Mu opioid receptor, and HIV-1 expression in the HIV-1 transgenic rat
Royal, W; Wang, HY; Jones, O; Tran, H; Bryant, JL
Journal of Neuroimmunology, 185(): 29-36.
Proceedings of the National Academy of Sciences of the United States of America
Dual effect of interleukin 4 on HIV-1 expression: Implications for viral phenotypic switch and disease progression
Valentin, A; Lu, WH; Rosati, M; Schneider, R; Albert, J; Karlsson, A; Pavlakis, GN
Proceedings of the National Academy of Sciences of the United States of America, 95(): 8886-8891.

Inflammation Research
JTE-607, a novel inflammatory cytokine synthesis inhibitor without immunosuppression, protects from endotoxin shock in mice
Kakutani, M; Takeuchi, K; Waga, I; Iwamura, H; Wakitani, K
Inflammation Research, 48(8): 461-468.

Immunological benefits of antiretroviral therapy in very early stages of asymptomatic chronic HIV-1 infection
Plana, M; Garcia, F; Gallart, T; Tortajada, C; Soriano, A; Palou, E; Maleno, MJ; Barcelo, JJ; Vidal, C; Cruceta, A; Miro, JM; Gatell, JM
AIDS, 14(): 1921-1933.

Journal of Clinical Investigation
Inducible targeting of IL-13 to the adult lung causes matrix metalloproteinase-and cathepsin-dependent emphysema
Zheng, T; Zhu, Z; Wang, ZD; Homer, RJ; Ma, B; Riese, RJ; Chapman, HA; Shapiro, SD; Elias, JA
Journal of Clinical Investigation, 106(9): 1081-1093.

European Journal of Pharmacology
JTE-607, a cytokine release blocker, attenuates acid aspiration-induced lung injury in rats
Jian, MY; Koizumi, T; Tsushima, K; Kubo, K
European Journal of Pharmacology, 488(): 231-238.
Antibody response to the surface envelope of caprine arthritis-encephalitis lentivirus: disease status is predicted by SU antibody isotype
Trujillo, JD; Hotzel, KJ; Snekvik, KR; Cheevers, WP
Virology, 325(1): 129-136.
Journal of Medical Virology
Relationship of in vivo and ex vivo levels of T(H)1 and T(H)2 cytokines with viremia in HAART patients with and without opportunistic infections
Sindhu, S; Toma, E; Cordeiro, P; Ahmad, R; Morisset, R; Menezes, J
Journal of Medical Virology, 78(4): 431-439.
AIDS Research and Human Retroviruses
A primer on HIV type 1-specific immune function and Remune (TM)
Moss, RB; Giermakowska, WK; Savary, JR; Theofan, G; Daigle, AE; Richieri, SP; Jensen, FC; Carlo, DJ
AIDS Research and Human Retroviruses, 14(): S167-S175.

American Journal of Tropical Medicine and Hygiene
In vitro production of type 1 and type 2 cytokines by peripheral blood mononuclear cells from subjects coinfected with human immunodeficiency virus and Leishmania infantum
Nigro, L; Cacopardo, B; Preiser, W; Braner, J; Cinatl, J; Palermo, F; Russo, R; Doerr, HW; Nunnari, A
American Journal of Tropical Medicine and Hygiene, 60(1): 142-145.

Microbes and Infection
Plasma interleukin-18 is associated with viral load and disease progression in HIV-1-infected patients
Wiercinska-Drapalo, A; Jaroszewicz, J; Flisiak, R; Prokopowicz, D
Microbes and Infection, 6(): 1273-1277.
Molecular Immunology
Role of cytokines and chemokines in the regulation of innate immunity and HIV infection
Alfano, M; Poli, G
Molecular Immunology, 42(2): 161-182.
Bmc Infectious Diseases
Immune responses in patients with HIV infection after vaccination with recombinant Hepatitis B virus vaccine
Pasricha, N; Datta, U; Chawla, Y; Singh, S; Arora, SK; Sud, A; Minz, RW; Saikia, B; Singh, H; James, I; Sehgal, S
Bmc Infectious Diseases, 6(): -.
Experimental and Molecular Pathology
Toll-like receptors, cytokines and HIV-1
Sanders, CM; Cruse, JM; Lewis, RE
Experimental and Molecular Pathology, 84(1): 31-36.
Journal of Neuroimmunology
Association of drug abuse with inhibition of HIV-1 immune responses: studies with long-term HIV-1 non-progressors
Nair, MPN; Mahajan, S; Hewitt, R; Whitney, ZRB; Schwartz, SA
Journal of Neuroimmunology, 147(): 21-25.
Scandinavian Journal of Immunology
Transforming growth factor-beta(1) suppresses interleukin-15-mediated interferon-gamma production in human T lymphocytes
Bonig, H; Banning, U; Hannen, M; Kim, YM; Verheyen, J; Mauz-Korholz, C; Korholz, D
Scandinavian Journal of Immunology, 50(6): 612-618.

Journal of Interferon and Cytokine Research
Expression of chemokine receptors on CD4(+) T cells in peripheral blood from HIV-infected individuals in Uganda
Oishi, K; Hayano, M; Yoshimine, H; Tugume, SB; Kebba, A; Mugerwa, R; Mugyenyi, P; Kumatori, A; Matsushima, K; Nagatake, T
Journal of Interferon and Cytokine Research, 20(6): 597-602.

Asian Pacific Journal of Allergy and Immunology
Flow cytometric detection of intracellular cytokines in peripheral blood of HIV-1 infected Thai children
Sukwit, S; Chuenchitra, T; Samakoses, R; Songprasom, K; Aree, C; Akapirat, S; Panjapornsuk, K; Ubol, S; Nitayaphan, S
Asian Pacific Journal of Allergy and Immunology, 19(2): 107-113.

Journal of Leukocyte Biology
IFN-gamma and IL-12 differentially regulate CC-chemokine secretion and CCR5 expression in human T lymphocytes
Losana, G; Bovolenta, C; Rigamonti, L; Borghi, I; Altare, F; Jouanguy, E; Forni, G; Casanova, JL; Sherry, B; Mengozzi, M; Trinchieri, G; Poli, G; Gerosa, F; Novelli, F
Journal of Leukocyte Biology, 72(4): 735-742.

Immunology Letters
Different mechanisms are utilized by HIV-1 Nef and staphylococcal enterotoxin A to control and regulate interleukin-10 production
Tangsinmankong, N; Day, NK; Good, RA; Haraguchi, S
Immunology Letters, 84(2): 97-101.
PII S0165-2478(02)00155-4
Haplotype diversity in the interleukin-4 gene is not associated with HIV-1 transmission and AIDS progression
Modi, WS; O'Brien, TR; Vlahov, D; Buchbinder, S; Gomperts, E; Phair, J; O'Brien, SJ; Winkler, C
Immunogenetics, 55(3): 157-164.
Journal of Immunology
HIV-1 gp120 induces IL-4 and IL-13 release from human Fc epsilon RI+ cells through interaction with the V(H)3 region of IgE
Patella, V; Florio, G; Petraroli, A; Marone, G
Journal of Immunology, 164(2): 589-595.

Journal of Infectious Diseases
Candida-specific systemic cell-mediated immune reactivities in human immunodeficiency virus-positive persons with mucosal candidiasis
Leigh, JE; Barousse, M; Swoboda, RK; Myers, T; Hager, S; Wolf, NA; Cutright, JL; Thompson, J; Sobel, JD; Fidel, PL
Journal of Infectious Diseases, 183(2): 277-285.

Cytokine responses to human immunodeficiency virus type I (HIV-1) induced by immunization with live recombinant canarypox virus vaccine expressing HIV-1 genes boosted by HIV-1(SF-2) recombinant GP120
Gorse, GJ; Patel, GB; Mandava, MD; Arbuckle, JA; Doyle, TM; Belshe, RB
Vaccine, 19(): 1806-1819.

Journal of General Virology
Co-expression of interleukin-5 influences replication of simian/human immunodeficiency viruses in vivo
Kozyrev, LL; Miura, T; Takemura, T; Kuwata, T; Ui, M; Buki, K; Iida, T; Hayami, M
Journal of General Virology, 83(): 1183-1188.

Antigen-specific cytokine response to hepatitis C virus core epitopes in HIV/hepatitis C virus-coinfected patients
Woitas, RP; Rockstroh, JK; Beier, I; Jung, G; Kochan, B; Matz, B; Brackmann, HH; Sauerbruch, T; Spengler, U
AIDS, 13(): 1313-1322.

Human Immunology
Differential modulation of CCR5-tropic human immunodeficiency virus-1 transfer from macrophages towards T cells under interleukin-4/interleukin-13 microenvironment
Saidi, H; Carbonneil, C; Magri, G; Eslahpazir, J; Sekaly, RP; Belec, L
Human Immunology, 71(1): 1-13.
Clinical and Experimental Immunology
Single-cell analysis of lymphokine imbalance in asymptomatic HIV-1 infection: evidence for a major alteration within the CD8(+) T cell subset
Sousa, AE; Victorino, RMM
Clinical and Experimental Immunology, 112(2): 294-302.

Upregulation of Fas ligand secretion in non-lymphopenic stages of HIV-1 infection
Silvestris, F; Camarda, G; Cafforio, P; Dammacco, F
AIDS, 12(9): 1103-1104.

International Immunology
CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients
Legendre, C; Raphael, M; Gras, G; Lefevre, EA; Feuillard, J; Dormont, D; Richard, Y
International Immunology, 10(): 1847-1851.

American Journal of Respiratory and Critical Care Medicine
Helper T cell type 1 and 2 cytokines regulate C-C chemokine expression in mouse pleural mesothelial cells
Mohammed, KA; Nasreen, N; Ward, MJ; Antony, VB
American Journal of Respiratory and Critical Care Medicine, 159(5): 1653-1659.

American Journal of Gastroenterology
Increased frequency of interferon-gamma-producing peripheral blood CD4(+) T cells in chronic hepatitis C virus infection
Kawakami, Y; Nabeshima, S; Furusyo, N; Sawayama, Y; Hayashi, J; Kashiwagi, S
American Journal of Gastroenterology, 95(1): 227-232.

Journal of Endodontics
Comparison of type 1 and type 2 cytokine production by mononuclear cells cultured with Streptococcus mutans and selected other caries bacteria
Hahn, CL; Best, AM; Tew, JG
Journal of Endodontics, 30(5): 333-338.

Journal of Theoretical Biology
HIV may produce inhibitory microRNAs (miRNAs) that block production of CD28, CD4 and some interleukins
Couturier, JP; Root-Bernstein, RS
Journal of Theoretical Biology, 235(2): 169-184.
Reversal of Aging: Resetting the Pineal Clock
Immunomodulation by immunopeptides and autoantibodies in aging, autoimmunity, and infection
Marchalonis, JJ; Schluter, SF; Sepulveda, RT; Watson, RR; Larson, DF
Reversal of Aging: Resetting the Pineal Clock, 1057(): 247-259.

Immunology and Cell Biology
Hepatitis C virus genotype and HIV coinfection affect cytokine mRNA levels in unstimulated PBMC but do not shift the T1/T2 balance
Lee, S; Watson, MW; Clark, B; Flexman, JP; Cheng, W; French, MA; Price, P
Immunology and Cell Biology, 84(4): 390-395.
Clinical Immunology
Normalized CD8+ but not CD4+ lymphocyte IL-2 expression is associated with early treatment with highly active antiretroviral therapy
Akerele, T; Galatowicz, G; Bunce, C; Calder, V; Lynn, WA; Lightman, S
Clinical Immunology, 121(2): 191-197.
Clinical and Vaccine Immunology
Lymphoproliferative and Cytokine Responses to Cryptosporidium parvum in Patients Coinfected with C-parvum and Human Immunodeficiency Virus
Kaushik, K; Khurana, S; Wanchu, A; Malla, N
Clinical and Vaccine Immunology, 16(1): 116-121.
Journal of Immunology
HIV-specific IL-10-positive CD8(+) T cells are increased in advanced disease and are associated with decreased HIV-specific cytolysis
Elrefaei, M; Barugahare, B; Ssali, F; Mugyenyi, P; Cao, H
Journal of Immunology, 176(2): 1274-1280.

Journal of Immunology
HIV-1 tat suppresses gp120-specific T cell response in IL-10-dependent manner
Gupta, S; Boppana, R; Mishra, GC; Saha, B; Mitra, D
Journal of Immunology, 180(1): 79-88.

HIV-associated dysfunction of in vitro IL-12 production depends on the nature of the stimulus and on the CD4 T-cell count of the patient
Vanham, G; Penne, L; Fransen, K; Kestens, L; De Brabander, M
Blood, 95(6): 2185-2187.

Journal of Infectious Diseases
Cellular immune responses of schistosomiasis patients are altered by human immunodeficiency virus type 1 coinfection
Mwinzi, PNM; Karanja, DMS; Colley, DG; Orago, ASS; Secor, WE
Journal of Infectious Diseases, 184(4): 488-496.

Journal of Medical Primatology
Expression of IFN-gamma induced CXCR3 agonist chemokines and compartmentalization of CXCR3(+) cells in the periphery and lymph nodes of rhesus macaques during simian immunodeficiency virus infection and acquired immunodeficiency syndrome
Sarkar, S; Kalia, V; Murphey-Corb, M; Montelaro, RC; Reinhart, TA
Journal of Medical Primatology, 32(): 247-264.

Virus Genes
The changes in the T helper 1 (Th1) and T helper 2 (Th2) cytokine balance during HIV-1 infection are indicative of an allergic response to viral proteins that may be reversed by Th2 cytokine inhibitors and immune response modifiers - A review and hypothesis
Becker, Y
Virus Genes, 28(1): 5-18.

Journal of Immunology
Kinetics of the changes of lymphocyte subsets defined by cytokine production at single cell level during highly active antiretroviral therapy for HIV-1 infection
Sousa, AE; Chaves, AF; Doroana, M; Antunes, F; Victorino, RMM
Journal of Immunology, 162(6): 3718-3726.

Cellular Immunology
Epinephrine-induced mobilization of natural killer (NK) cells and NK-like T cells in HIV-infected patients
Sondergaard, SR; Ullum, H; Skinhoj, P; Pedersen, BK
Cellular Immunology, 197(2): 91-98.

Clinical and Experimental Immunology
Human T cells with a type-2 cytokine profile are resistant to apoptosis induced by primary activation: consequences for immunopathogenesis
Carbonari, M; Tedesco, T; Del Porto, P; Paganelli, R; Fiorilli, M
Clinical and Experimental Immunology, 120(3): 454-462.

Clinical Immunology
Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAART
Sousa, AE; Chaves, AF; Doroana, M; Antunes, F; Victorino, RMM
Clinical Immunology, 97(2): 162-170.

Th1/Th2 shift in HIV lymph nodes: No contribution of CD60 cells
Bogner, JR; Walli, R; Goebel, FD
Infection, 29(1): 32-36.

Journal of Virology
Targeting c-Mpl for revival of human immunodeficiency virus type 1-induced hematopoietic inhibition when CD34(+) progenitor cells are re-engrafted into a fresh stromal microenvironment in vivo
Koka, PS; Kitchen, CMR; Reddy, ST
Journal of Virology, 78(): 11385-11392.

Journal of Virology
Gastrointestinal T lymphocytes retain high potential for cytokine responses but have severe CD4(+) T-cell depletion at all stages of simian immunodeficiency virus infection compared to peripheral lymphocytes
Smit-McBride, Z; Mattapallil, JJ; McChesney, M; Ferrick, D; Dandekar, S
Journal of Virology, 72(8): 6646-6656.

Comparison of HCV-specific intrahepatic CD4+ T cells in HIV/HCV versus HCV
Graham, CS; Curry, M; He, Q; Afdhal, N; Nunes, D; Fleming, C; Horsburgh, R; Craven, D; Sherman, KE; Koziel, MJ
Hepatology, 40(1): 125-132.
Jama-Journal of the American Medical Association
Etiology of pruritic papular eruption with HIV infection in Uganda
Resneck, JS; Van Beek, M; Furmanski, L; Oyugi, J; LeBoit, PE; Katabira, E; Kambugu, F; Maurer, T; Berger, T; Pletcher, MJ; Machtinger, EL
Jama-Journal of the American Medical Association, 292(): 2614-2621.

Journal of Infectious Diseases
CD4(+) T cell-dependent reduction in hepatitis C virus-specific humoral immune responses after HIV infection
Netski, DM; Mosbruger, T; Astemborski, J; Mehta, SH; Thomas, DL; Cox, AL
Journal of Infectious Diseases, 195(6): 857-863.
Journal of Virology
Gamma/delta T-cell functional responses differ after pathogenic human immunodeficiency virus and nonpathogenic simian immunodeficiency virus infections
Kosub, DA; Lehrman, G; Milush, JM; Zhou, DJ; Chacko, E; Leone, A; Gordon, S; Silvestri, G; Else, JG; Keiser, P; Jain, MK; Sodora, DL
Journal of Virology, 82(3): 1155-1165.
Clinical Immunology
Enhanced IFN-gamma production in vitro by CD8(+) T cells in hemophiliacs with AIDS as demonstrated on the single-cell level
Pae, Y; Minagawa, H; Hayashi, J; Kashiwagi, S; Yanagi, Y
Clinical Immunology, 92(1): 111-117.

Clinical and Experimental Immunology
Decreased CD40 ligand induction in CD4 T cells and dysregulated IL-12 production during HIV infection
Vanham, G; Penne, L; Devalck, J; Kestens, L; Colebunders, R; Bosmans, E; Thielemans, K; Ceuppens, JL
Clinical and Experimental Immunology, 117(2): 335-342.

Clinics in Dermatology
Natural history of HIV-1 infection
Touloumi, G; Hatzakis, A
Clinics in Dermatology, 18(4): 389-399.

American Journal of Respiratory and Critical Care Medicine
Innate immune system damage in human immunodeficiency virus type 1 infection - Implications for acquired immunity and vaccine design
Howie, S; Ramage, R; Hewson, T
American Journal of Respiratory and Critical Care Medicine, 162(4): S141-S145.

Molecular Immunology
Site A of the MCP-1 distal regulatory region functions as a transcriptional modulator through the transcription factor NF1
Kumar, SN; Boss, JM
Molecular Immunology, 37(): 623-632.

British Journal of Haematology
Reciprocal alterations of Th1/Th2 function in gamma delta T-cell subsets of human immunodeficiency virus-1-infected patients
Dobmeyer, TS; Dobmeyer, R; Wesch, D; Helm, EB; Hoelzer, D; Kabelitz, D
British Journal of Haematology, 118(1): 282-288.

Acta Dermato-Venereologica
Role of Th2 cytokines, RANTES and eotaxin in AIDS-associated eosinophilic folliculitis
Amerio, P; Verdolini, R; Proietto, G; Feliciani, C; Toto, P; Shivji, G; Loconsole, F; Cassano, N; Amerio, P; Vena, G; Sauder, DN
Acta Dermato-Venereologica, 81(2): 92-95.

Journal of Immunology
Follicular dendritic cell-mediated up-regulation of CXCR4 expression on CD4 T cells and HIV pathogenesis
Estes, JD; Keele, BF; Tenner-Racz, K; Racz, P; Redd, MA; Thacker, TC; Jiang, YJ; Lloyd, MJ; Gartner, S; Burton, GF
Journal of Immunology, 169(5): 2313-2322.

Current HIV Research
Cytopenias in HIV infection: Mechanisms and alleviation of hematopoietic inhibition
Koka, PS; Reddy, ST
Current HIV Research, 2(3): 275-282.

Journal of Leukocyte Biology
Skewed expression and up-regulation of the IL-12 and IL-18 receptors in resting and activated CD4 T cells from HIV-1-infected patients
de Arquer, GR; Pena, R; Cabrera, C; Coma, G; Ruiz-Hernandez, R; Guerola, R; Clotet, B; Ruiz, L; Este, JA; Calle, ML; Bofill, M
Journal of Leukocyte Biology, 82(1): 72-78.
Molecular Pharmacology
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Journal of Infectious Diseases
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Journal of Neuroimmunology
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International Journal of Dermatology
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Best Practice & Research Clinical Endocrinology & Metabolism
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Archives of Virology
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Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology
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Cellular Immunology
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Journal of Acquired Immune Deficiency Syndromes
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Scandinavian Journal of Infectious Diseases
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Scandinavian Journal of Infectious Diseases, 32(6): 597-603.

Transactions of the Royal Society of Tropical Medicine and Hygiene
Antileishmanial antibodies in an outbreak of visceral leishmaniasis in eastern Sudan: high antibody responses occur in resistant subjects and are not predictive of disease
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Journal of Allergy and Clinical Immunology
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Chinese Medical Journal
Different plasma levels of interleukins and chemokines: comparison between children and adults with AIDS in China
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International Immunology
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Expression Levels of TLRs Involved in Viral Recognition in PBMCs from HIV-1-Infected Patients Failing Antiretroviral Therapy
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Journal of Immunology
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Journal of Immunology, 161(7): 3219-3223.

Journal of Clinical Immunology
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Asian Pacific Journal of Allergy and Immunology
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Journal of Immunology
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Journal of Infectious Diseases
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Journal of Biochemistry
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Impaired progenitor cell function in HIV-negative infants of HIV-positive mothers results in decreased thymic output and low CD4 counts
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European Journal of Clinical Microbiology & Infectious Diseases
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Mechanisms of protection induced by attenuated simian immunodeficiency virus - V. No evidence for lymphocyte-regulated cytokine responses upon rechallenge
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B7-H1 is up-regulated in HIV infection and is a novel surrogate marker of disease progression
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Activation of the formyl peptide receptor by the HIV-derived peptide T-20 suppresses interleukin-12 p70 production by human monocytes
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Journal of Immunology
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Chan, WL; Pejnovic, N; Lee, CA; Al-Ali, NA
Journal of Immunology, 167(3): 1238-1244.

A nonsecreted variant of interleukin-4 is associated with apoptosis: implication for the T helper-2 polarization in HIV infection
Ledru, E; Fevrier, M; Lecoeur, H; Garcia, S; Boullier, S; Gougeon, ML
Blood, 101(8): 3102-3105.
Journal of Leukocyte Biology
IL-4 and a glucocorticoid up-regulate CXCR4 expression on human CD4(+) T lymphocytes and enhance HIV-1 replication
Wang, JB; Harada, A; Matsushita, S; Matsumi, S; Zhang, Y; Shioda, T; Nagai, Y; Matsushima, K
Journal of Leukocyte Biology, 64(5): 642-649.

Highly increased numbers of leukocytes in inflamed gingiva from patients with HIV infection
Myint, M; Steinsvoll, S; Yuan, ZN; Johne, B; Helgeland, K; Schenck, K
AIDS, 16(2): 235-243.

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Monocytes and T lymphocytes in HIV-1-positive patients express HLA-G molecule
Lozano, JM; González, R; Kindelán, JM; Rouas-Freiss, N; Caballos, R; Dausset, J; Carosella, ED; Peña, J
AIDS, 16(3): 347-351.

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Impaired production of cytokines is an independent predictor of mortality in HIV-1-infected patients
Ostrowski, SR; Gerstoft, J; Pedersen, BK; Ullum, H
AIDS, 17(4): 521-530.

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HIV+ elite controllers have low HIV-specific T-cell activation yet maintain strong, polyfunctional T-cell responses
Deeks, SG; Norris, PJ; the NIAID Center for HIV/AIDS Vaccine Immunology, ; Owen, RE; Heitman, JW; Hirschkorn, DF; Lanteri, MC; Biswas, HH; Martin, JN; Krone, MR
AIDS, 24(8): 1095-1105.
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Inverse association of repressor growth factor independent-1 with CD8 T cell interleukin (IL)-7 receptor α expression and limited signal transducers and activators of transcription signaling in response to IL-7 among γ-chain cytokines in HIV patients
Benoit, A; Abdkader, K; Sirskyj, D; Alhetheel, A; Sant, N; Diaz-Mitoma, F; Kumar, A; Kryworuchko, M
AIDS, 23(11): 1341-1347.
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Back to Top | Article Outline

AIDS; cytokines; cytoplasmic cytokine detection; FACS; HIV; Th1 cytokines; Th2 cytokines

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