Recirculating HIV-target T lymphocytes at the mucosal surface of the female genital tract are associated with progesterone increases during the menstrual cycle (MUC2P.938)

Abstract

Abstract The Female Genital Tract (FGT) provides a means of entry to opportunistic infections, including HIV, yet immune cell populations at this mucosal surface are poorly defined. We initiated a study of 20 healthy women to characterize resident T cell populations in the lower FGT from lavage and patient-matched blood samples. Surprisingly, we report FGT T cells were primarily CCR7hi memory CD4 T cells (P=<0.0001), consistent with a central memory phenotype and known HIV reservoir. FGT CCR7hi T cells exhibited more frequent expression of HIV susceptibility markers CCR5 and CD38 compared to blood (0.6% vs. 13.6%, P=0.0017), yet retained the ability to migrate to CCR7 ligands, suggesting these cells could migrate from the genital tract into afferent lymphatics. Finally, we demonstrate the frequency of FGT CCR7hi target cells increased during the luteal phase of the menstrual cycle (51.7-72.7), and correlated to progesterone from patient-matched blood (r=0.5176, P=0.0024). These data show that a majority of CD4 T cells at the surface of the FGT in humans do not express canonical resident memory T cell markers, but are primarily a central memory T cell phenotype with the ability to traffic across the mucosal epithelium into underlying tissue. Our findings suggest HIV may directly infect recirculating memory CD4 T cells that traffic virus across the FGT mucosal barrier and progesterone changes throughout the menstrual cycle may predict availability of these cells HIV target cells.