Mucosal and systemic γδ⁺ T cells associated with control of simian immunodeficiency virus infection

γδ T cells act as a first line of defense against invading pathogens. However, despite their abundance in mucosal tissue, little information is available about their functionality in this compartment in the context of HIV/SIV infection. In this study, we evaluated the frequency, phenotype, and functionality of Vδ1 and Vδ2 T cells from blood, rectum, and the female reproductive tract (FRT) of rhesus macaques to determine whether these cells contribute to control of SIV infection. No alteration in the peripheral Vδ1/Vδ2 ratio in SIV-infected macaques was observed. However, CD8⁺ and CD4⁺CD8⁺ Vδ1 T cells were expanded along with upregulation of NKG2D, CD107, and granzyme B, suggesting cytotoxic function. In contrast, Vδ2 T cells showed a reduced ability to produce the inflammatory cytokine IFN-γ. In the FRT of SIV⁺ macaques, Vδ1 and Vδ2 showed comparable levels across vaginal, ectocervical, and endocervical tissues; however, endocervical Vδ2 T cells showed higher inflammatory profiles than the two other regions. No sex difference was seen in the rectal Vδ1/Vδ2 ratio. Several peripheral Vδ1 and/or Vδ2 T cell subpopulations expressing IFN-γ and/or NKG2D were positively correlated with decreased plasma viremia. Notably, Vδ2 CD8⁺ T cells of the endocervix were negatively correlated with chronic viremia. Overall, our results suggest that a robust Vδ1 and Vδ2 T cell response in blood and the FRTof SIV-infected macaques contribute to control of viremia.