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 CD161CD8 T cells in the macaque model of HIV infection. In contrast to the significant loss of CD161CD4 T cells, CD161CD8 T cell frequencies were maintained in blood and gut during chronic SIV infection. Furthermore, gut CD161CD8 T cells displayed greater IL-17 production and maintained Th1-type and cytolytic functions, contrary to impaired IL-17 and granzyme-B production in CD161CD4 T cells of SIV-infected macaques. These results suggest that augmented Th17-type effector functions of CD161CD8 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 CD161CD8 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.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535321PMC
http://dx.doi.org/10.3390/v15091944DOI Listing

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