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* Division of Infectious Diseases, University of California, San Francisco, CA 94143;
Joint Clinical Research Centre, Kampala, Uganda; and
California Department of Health Services, Richmond, CA 94804
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.
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