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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.

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+CD161(high)Tc17 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+CD161(high)Tc17 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.