Common and divergent features of T cells from blood, gut, and genital tract of ART-treated HIV+ women

CD4+ and CD8+ T cells in mucosal tissues play important roles in homeostasis and defense against invading microbial pathogens. The gut and female reproductive tract (FRT) are both tolerogenic environments, but differ in the kinds of non-self antigens they need to tolerate. How these different mucosal environments influence the properties of their respective resident T cells is poorly understood but important for better understanding women's health. We recruited ART-suppressed women living with HIV (WLWH) who donated within the same study visit blood, and biopsies from the ileum, colon, rectosigmoid, endometrium, endocervix, and ectocervix, from which we conducted 36-parameter phenotyping of T cells by CyTOF. Although gut and FRT T cells shared features discriminating them from the blood counterparts, they also harbored features distinguishing them from one another including preferential expression of the Trm markers CD69 and CD103 on the gut-derived cells. CD69+CD103+ CD8+ T cells from FRT, but not those from gut, preferentially expressed PD1. We further determined that a recently described population of CXCR4+ T inflammatory mucosal (Tim) cells differentially expressed other chemokine receptors relative to their blood counterparts. Our findings support the emerging concept that T cells resident in different tolerogenic mucosal sites take on distinct properties.