Enhanced Th1/Th17 Functions of CD161(+) CD8(+) T Cells in Mucosal Tissues of Rhesus Macaques

Expression of the C-type lectin-like receptor CD161 by human T cells is associated with type-17 responses, which play critical regulatory roles in immunity and inflammation at mucosal sites. However, the functions of CD161-expressing T cells in macaques, the pre-clinical model of several human diseases, remain unknown. This study examined the phenotypic and functional characteristics of CD161(+) T cells in peripheral blood, mucosal tissues and lymph nodes of rhesus macaques. Majority of CD161-expressing T cells in peripheral blood and lung/intestinal mucosal tissues of rhesus macaques were found to be CD8(+)CD4(–) in phenotype. There was a significant enrichment of CD161(+)CD8(+) T cells in the lungs and colonic mucosa (16.1%±6.6 and 16.8%±5.7) in comparison to peripheral blood (4.2%±1.2) and mesenteric lymph nodes (1.3%±0.8). Regardless of the tissue compartment, CD161(+)CD8(+) T cells mainly comprised of γδ T cells and TCR Vα7.2(+) MAIT cells (up to 80%), and displayed Th1 and Th17 cytokine responses to mitogen stimulation. Mucosal CD161(+)CD8(+) T cells were characterized by very high expression of CD69, a recent activation marker that is preferentially expressed on tissue resident cells. Furthermore, lung and colonic mucosal CD161(+)CD8(+) T cells showed enhanced IFN-γ, IL-17, and Perforin production in comparison to those in blood. Thus, macaque CD161(+)CD8(+) T cells represent mucosal tissue-homing innate-like CD8(+) T-cell populations with Th1/Th17 type cytokine and cytotoxic effector functions that can potentially enhance the recruitment of adaptive immune cells and control initial pathogen burden/dissemination in tissues. Analysis of their role in early immune responses to mucosal pathogens will be valuable in the design of vaccines and therapeutics.