Our research centers on the impact of cytolytic CD4+ T cells in HIV-1 disease pathogenesis. Cytolytic CD4+ T cells, otherwise known as effector CD4+ cells, behave very much like effector CD8+ T cells (CTL), in that they directly mediate the lysis of infected cells ex vivo. CD4+ T cells engage their targets in an MHC restricted, HIV-specific manner, requiring perforin, and cell-cell contact for target cell elimination. The full potential of HIV-specific effector CD4+ T cells in HIV pathogenesis is not well understood, however elite long-term non-progressors, who are able to control virus and maintain normal numbers of CD4+ T cells in the absence of anti-retroviral therapy, have a higher frequency of HIV-specific effector CD4+ T cells than persons who progress more rapidly to AIDS. Our investigations endeavor to establish the mechanism by which effector CD4+ T cells contribute toward delayed disease progression in HIV infected persons.