Regulatory T Cells Kinetics in Immune Reconstitution Inflammatory Syndrome in HIV-Tuberculosis Co-Infected Individuals

Abstract

Background: Combination antiretroviral therapy (cART) can suppress human immunodeficiency virus (HIV-1) replication, but some patients develop worsening of co-infections, termed immune reconstitution inflammatory syndrome. Regulatory T cells (Tregs) are a population of CD4+ T cells that modulate immune responses. We hypothesized that immune reconstitution inflammatory syndrome (IRIS) is associated with Tregs dysfunction. Methods: We prospectively enrolled antiretroviral naive HIV patients with co-infection with Mycobacterium tuberculosis (MTB; N = 26) or controls with no prior opportunistic infection (N = 10). We prospectively measured HIV viral load, CD4+ T cell count, regulatory T cell (CD4high, CD127low-neg, Foxp3+) proportion, and Interferon-γ (IFN-γ) response to MTB peptides before and after initiation of combination antiretroviral therapy. Results: Eleven of the MTB patients developed IRIS; 15 did not. IRIS patients had a lower proportion of Tregs at baseline compared to no-IRIS patients (HIV/no-OI and HIV/MTB no-IRIS), but the difference did not reach statistical significance (IRIS: 9.6 [5.3-11.2]; no-IRIS: 13.9 [7.6-22.5] p = 0.066). After 2 weeks of cART the proportion of Tregs was significantly lower in HIV/MTB IRIS patients (HIV/MTB IRIS: 9.8 [6.6-13.6], HIV/MTB no-IRIS: 15.8 [11.1-18.8]. The antigen-specific IFN-γ production was greater in the patients who developed IRIS compared with those who did not develop IRIS. Conclusion: IRIS patients had a lower proportion of Tregs and more marked IFN-γ production, suggesting that Tregs may be responsible for suppressing the antigen-specific inflammatory response.