Characterization of HIV-1-Specific Cytotoxic T Lymphocytes Expressing the Mucosal Lymphocyte Integrin CD103 in Rectal and Duodenal Lymphoid Tissue of HIV-1-Infected Subjects

AbstractAcute HIV-1 infection depletes CD4+ T cells in gut-associated lymphoid tissue (GALT). The failure of containment of local viral replication, and consequent CD4+ T cell depletion, might be due to delayed mobilization of effector CD8+ T cells or absence of functioning HIV-1-specific CD8+ T cell effectors within GALT. No studies have addressed human intestinal HIV-1-specific CD8+ T cell functions. We sought to determine whether functional HIV-1-specific CTL were present in GALT and whether the repertoire differed from HIV-1-specific CTL isolated from peripheral blood mononuclear cells. From three HIV-1-infected subjects, we isolated HIV-1-specific CD8+ T cells expressing the mucosal lymphocyte integrin CD103 from GALT. These antigen-specific effector cells could be expanded in vitro and lysed target cells in an MHC class I-restricted manner. HIV-1-specific CTL could be isolated from both duodenal and rectal GALT sites, indicating that CD8+ effectors were widespread through GALT tissue. The breadth and antigenic specificities of GALT CTL appeared to differ from those in peripheral blood in some cases. In summary, we found HIV-1-specific CD8+ effector T cells in GALT, despite HIV-1-induced CD4+ T cell lymphopenia. This suggests that HIV-1-specific CTL in gut tissue can be maintained with limited CD4+ T cell help