Enhanced IL-17 Producing and Maintained Cytolytic Effector Functions of Gut Mucosal CD161(+)CD8(+) T Cells in SIV-Infected Rhesus Macaques

Previous studies have indicated that the loss of CD161-expressing CD4(+) Th17 cells is linked to the progression of chronic HIV. These cells are significantly depleted in peripheral blood and gut mucosa of HIV-infected individuals, contributing to inflammation and disruption of the gut barrier. However, the impact of HIV infection on CD161-expressing CD8(+) T cells remain unclear. Here, we examined the functions of peripheral blood and mucosal CD161(+)CD8(+) T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161(+)CD4(+) T cells, CD161(+)CD8(+) T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161(+)CD8(+) T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161(+)CD4(+) T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161(+)CD8(+) T cells during SIV infection is a likely mechanism to compensate for the sustained loss of gut mucosal Th17 cells. Targeting the cytokine and cytolytic effector functions of CD161(+)CD8(+) T cells in the preclinical setting of chronic SIV infection with antiretroviral therapy has implications in the restoration of gut barrier disruption in persons with HIV infection.