CD8+ T suppressor lymphocytes have been described. However, the regulatory role of IL-10+ CD8+ Ts in modulating HIV-specific T cell responses remains unknown. The aims proposed in this research plan contain a series of experiments designed to explore the role of HIV-specific IL-10+ CD8+ T cells in mediating T cell immune dysfunction in HIV infection. I hypothesize that HIV-specific IL-10+ CD8+ T cells exert an inhibitory effect on distinct populations of HIV-specific effector T cells. Aim 1 explores the mechanisms of suppression utilized by the IL-10+ CD8+ Ts during HIV infection. The role of 1) contact dependent suppression, 2) cytokines such as IL-10 and TGF-beta, will be examined. Aim 2 investigates the phenotypic characteristics and specificity of the IL-10+ CD8+ Ts during HIV infection. This aim will focus on examining the suppressive effect of the IL-10+ CD8+ Ts to different HIV, and non-HIV-specific effector T cells. The expression by the IL- 10+ CD8+ Ts of various markers associated with regulatory T cells, such as CD25, FoxpS, CTLA-4 will also be assessed.