HIV-specific regulatory T cells are associated with higher CD4 cell counts in primary infection

Kared, Hassena; Lelièvre, Jean-Daniela,b,c; Donkova-Petrini, Vladimiraa; Aouba, Albertined; Melica, Giovannab,c; Balbo, Michèlea; Weiss, Laurencea,d,e; Lévy, Yvesa,b,c

doi: 10.1097/QAD.0b013e328319edc0
Basic Science

Objective: Expansion of regulatory T (Treg) cells has been described in chronically HIV-infected individuals. We investigated whether HIV-suppressive Treg could be detected during primary HIV infection (PHI).

Methods: Seventeen patients diagnosed early after PHI (median: 13 days; 1–55) were studied. Median CD4 cell count was 480 cells/μl (33–1306) and plasma HIV RNA levels ranged between 3.3 and 5.7 log10 copies/ml. Suppressive capacity of blood purified CD4+CD25+ was evaluated in a coculture assay. Fox-p3, IL-2 and IL-10 were quantified by reverse transciptase (RT)-PCR and intracellular staining of ex vivo and activated CD4+CD25high T cells.

Results: The frequency of CD4+CD127lowCD25high T cells among CD4 T cells was lower in patients with PHI compared with chronic patients (n = 19). They exhibited a phenotype of memory T cells and expressed constitutively FoxP3. Similar to chronic patients, Treg from patients with PHI inhibited the proliferation of purified tuberculin (PPD) and HIV p24 activated CD4+CD25 T cells. CD4+CD25high T cells from patients with PHI responded specifically to p24 stimulation by expressing IL-10. In untreated patients with PHI, the frequency as well as HIV-specific activity of Treg decreased during a 24-month follow-up. A positive correlation between percentages of Treg and both CD4 cell counts and the magnitude of p24-specific suppressive activity at diagnosis of PHI was found.

Conclusion: Our data showed that HIV drives Treg, as PHI and these cells persist throughout the course of the infection. A correlation between the frequency of Treg and CD4 T-cell counts suggest that these cells may impact on the immune activation set point at PHI diagnosis.

Author Information

aINSERM, Unite U841, France

bUniversite Paris 12, Faculte de Medecine, France

cAP-HP, Groupe Henri-Mondor Albert-Chenevier, Immunologie clinique, Creteil, France

dAP-HP, Hôpital Européen Georges Pompidou, Immunologie clinique, France

eUniversité Paris Descartes, Faculté de Médecine, Paris, France.

Received 7 September, 2008

Accepted 8 September, 2008

Correspondence to Professor Y. Lévy, Service d'Immunologie Clinique, Hôpital Henri Mondor and INSERM U841 and University Paris 12, Créteil, France. Tel: +33 1 49 81 24 55; fax: +33 1 49 81 24 69; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.