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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000173
Basic and Translational Science

Regulatory T Cells in HIV-Infected Immunological Nonresponders Are Increased in Blood but Depleted in Lymphoid Tissue and Predict Immunological Reconstitution

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

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Abstract

Background: HIV-infected immunological nonresponders fail to immune reconstitute despite optimal treatment. We hypothesized that regulatory T cells (Tregs) are involved in immunological reconstitution. Tregs and Treg subpopulations were measured in blood and Foxp3+ cells in lymphoid tissue, and the impact of Tregs on immunological reconstitution was determined.

Methods: HIV-infected individuals on combination antiretroviral therapy for a minimum of 2 years were included. The study population included 14 immunological nonresponders (INR; CD4 T-cell count <200 cells/μL), 33 intermediate responders (CD4 T-cell count 200–500 cells/μL), 30 responders (CD4 T-cell count >500 cells/μL), and 34 healthy controls. Tregs, Treg subpopulations, and intracellular staining for interleukin 10 in peripheral blood were measured using flow cytometry. Foxp3+ cells in lymphoid tissue were evaluated using immunolabeling. The CD4 T-cell count was determined at inclusion and after 1 year of follow-up.

Results: INR displayed high percentage of Tregs and activated Tregs in peripheral blood accompanied by a high percentage of Tregs expressing interleukin 10, whereas numbers of Foxp3+ cells in lymphoid tissue were low. In contrast, responders resembled healthy controls. Finally, in INR, high level of Tregs in blood and Foxp3+ cells in lymphoid tissue were associated with higher level of immunological reconstitution after 1 year of follow-up.

Conclusions: In conclusion, altered distribution of Tregs was found in INR. Interestingly, high level of Tregs predicted higher level of immunological reconstitution suggesting a role for Tregs in immunological reconstitution.

© 2014 by Lippincott Williams & Wilkins

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