(from abstract): The control of virus replication in primary HIV-1 infection and disease following infection are correlated with the magnitude of the CD8+ T lymphocyte response. The central role of this CD8+ lymphocyte mediated cellular immune response in controlling virus replication has recently been demonstrated directly using the simian immunodeficiency virus of macaques (SIVmac)/rhesus monkey model of AIDS. However, a more detailed characterization of the anatomic distribution and functions mediated by CD8+ lymphocytes is essential for developing strategies to prevent or treat HIV-1 infection. In particular, the mechanism by which virus replication is controlled, the anatomic distribution of these virus-specific CD8+ lymphocytes among various lymphoid tissues and the potential contribution of these cells to AIDS pathogenesis are not fully understood. This is an amended application proposing to explore the anatomic distribution of SIV-specific CTL and the role of CD8+lymphocytes in the immunopathogenesis of CD4+T cell decline in AIDS virus infection. Specifically, 1. Describe the anatomic distribution of SIVmac-specific CD8+ T lymphocytes in primary infection and 2. Determine the contribution of CD8+ lymphocytes to the loss of CD4+ Tcells following infection by SIVmac or the rapidly CD4+T cell-depleting virus SHIV-KB9.
