Depletion of Regulatory T Cells in HIV Infection Is Associated with Immune Activation

TLDR

Immune activation during chronic HIV infection predicts death and may mediate CD4+ T cell depletion, while regulatory T cells (Tregs) are CD4+CD25brightCD62Lhigh cells that down‑regulate immune responses. The study aimed to determine whether loss of Tregs drives immune activation and to hypothesize that Treg skewing contributes to T cell effector dysfunction. The authors performed a cross‑sectional study of 81 HIV‑positive Ugandan volunteers. Treg numbers were strongly correlated with CD4+ and CD8+ T cell activation, a relationship stronger than viral load or CD4 count, and Tregs declined at a different rate than other CD4+ cells, increasing the regulator‑to‑helper ratio in advanced disease, indicating that Tregs are a major contributor to immune activation during chronic HIV infection.

Abstract

Abstract Immune activation during chronic HIV infection is a strong clinical predictor of death and may mediate CD4+ T cell depletion. Regulatory T cells (Tregs) are CD4+CD25brightCD62Lhigh cells that actively down-regulate immune responses. We asked whether loss of Tregs during HIV infection mediates immune activation in a cross-sectional study of 81 HIV-positive Ugandan volunteers. We found that Treg number is strongly correlated with both CD4+ and CD8+ T cell activation. In multivariate modeling, this relationship between Treg depletion and CD4+ T cell activation was stronger than any other clinical factor examined, including viral load and absolute CD4 count. Tregs appear to decline at different rates compared with other CD4+ T cells, resulting in an increased regulator to helper ratio in many patients with advanced disease. We hypothesize that this skewing may contribute to T cell effector dysfunction. Our findings suggest Tregs are a major contributor to the immune activation observed during chronic HIV infection.