CD4+ T cells within lymphoid tissue throughout the body represent the major site of HIV infection and the long-term HIV reservoir that prevents the development of an HIV cure and hampers vaccine development strategies. CD8+ T cell activity is thought to be responsible for controlling HIV replication, but our preliminary data indicates tht this activity is dysfunctional within lymphoid tissue. This proposal will define the function and dysfunction of lymphoid tissue CD8+ T cells in order to define strategies for eliminating HIV infection.