Abstract:
Gamma delta 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 V delta 1 and V delta 2 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 V delta 1/V delta 2 ratio in SIV-infected macaques was observed. However, CD8(+) and CD4(+) CD8(+) V delta 1 T cells were expanded along with upregulation of NKG2D, CD107, and granzyme B, suggesting cytotoxic function. In contrast, V delta 2 T cells showed a reduced ability to produce the inflammatory cytokine IFN-gamma. In the FRT of SIV + macaques, V delta 1 and V delta 2 showed comparable levels across vaginal, ectocervical, and endocervical tissues; however, endocervical V delta 2 T cells showed higher inflammatory profiles than the two other regions. No sex difference was seen in the rectal V delta 1/V delta 2 ratio. Several peripheral V delta 1 and/or V delta 2 T cell subpopulations expressing IFN-gamma and/or NKG2D were positively correlated with decreased plasma viremia. Notably, V delta 2 CD8(+) T cells of the endocervix were negatively correlated with chronic viremia. Overall, our results suggest that a robust V delta 1 and V delta 2 T cell response in blood and the FRTof SIV-infected macaques contribute to control of viremia.