Share this article on:

Immunoregulatory T Cells May Be Involved in Preserving CD4 T Cell Counts in HIV-Infected Long-Term Nonprogressors and Controllers

Gaardbo, Julie C. MD*,†; Ronit, Andreas BSc*,†; Hartling, Hans J. MD*,†; Gjerdrum, Lise M. R. MD, PhD; Springborg, Karoline MD§; Ralfkiær, Elisabeth MD; Thorsteinsson, Kristina MD; Ullum, Henrik MD, PhD; Andersen, Åse B. MD; Nielsen, Susanne D. MD, DMSc*

JAIDS Journal of Acquired Immune Deficiency Syndromes: January 1st, 2014 - Volume 65 - Issue 1 - p 10–18
doi: 10.1097/QAI.0b013e3182a7c932
Basic and Translational Science

Background: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell counts in controllers and in LTNPs.

Methods: Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17 cells, and CD3+CD8+CD161highTc17 cells in peripheral blood were measured using flow cytometry. Tregs in lymphoid tissue were determined in tonsil biopsies and evaluated using immunolabeling. The production of transforming growth factor beta (TGF-β), interleukin (IL)-10, and IL-17 upon stimulation with phytohemagglutinin in peripheral blood was determined by Luminex.

Results: All groups of HIV-infected patients displayed similar percentages of Tregs in both peripheral blood and lymphoid tissue. However, a larger percentage of Tregs in ECs and LTNPs were activated compared with that in controls, progressors, and viremic controllers. Further, ECs as the only group of HIV-infected patients, displayed elevated percentages of CD161+Th17 cells, preserved CD3+CD8+CD161highTc17 cells, and preserved IL-10 production.

Conclusions: Overall, Treg percentage was similar in both blood and lymphoid tissue in all groups of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors.

*Viro-Immunology Research Group, Departments of Infectious Diseases;

Clinical Immunology;

Pathology; and

§Oto-Rhinolaryngology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark;

Department of Infectious Diseases, Hvidovre Hospital, University Hospital of Copenhagen, Copenhagen, Denmark; and

Department of Infectious Diseases, Odense Hospital, University of Southern Denmark, Odense, Denmark.

Correspondence to: Susanne D. Nielsen, Department of Infectious Diseases, Rigshospitalet, University Hospital of Copenhagen, Copenhagen 2100, Denmark (e-mail: sdn@dadlnet.dk).

Supported by The Novo Nordisk Foundation, The Lundbeck Foundation, The Augustinus Foundation, The Danish AIDS Foundation, Rigshospitalet Research Council, and University of Copenhagen.

Part of the results have been presented at CROI, 20th Conference of Retroviruses and Opportunistic Infections, Atlanta, 2013.

The authors have no conflicts of interest to disclose.

J.C.G. designed the study, included the patients, performed the experiments, analyzed the results, and wrote the manuscript; A.R. included the patients, performed the experiments, and critically revised the manuscript; H.J.H. included the patients, performed the experiments, and critically revised the manuscript; L.M.R.G. stained the tonsil biopsies, analyzed the results, and critically revised the manuscript; K.S. performed the tonsil biopsies and critically revised the manuscript; K.T included the patients and critically revised the manuscript; H.U. supervised the work in the laboratory and critically revised the manuscript; Å.B.A. designed the study and critically revised the manuscript; S.D.N. was the principal investigator, designed the study, supervised data analysis, and critically revised the manuscript.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jaids.com).

Received May 02, 2013

Accepted July 30, 2013

© 2014 by Lippincott Williams & Wilkins