γδ T cells compose a developmentally regulated intrauterine population and protect against vaginal candidiasis

This most comprehensive analysis to date of gamma delta T cells in the murine uterus reveals them to compose a unique local T-cell compartment. Consistent with earlier reports, most cells expressed a canonical V gamma 6V delta 1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine gamma delta T cells were not obviously intraepithelial, being more akin to sub-epithelial V gamma 6V delta 1(+) T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-V gamma 6(+), IFN-gamma-producing cells; was strikingly enriched in young mice; expressed genes hitherto associated with the uterus, including the progesterone receptor; and did not require microbes for development and/or maintenance. This notwithstanding, gamma delta T-cell deficiency severely impaired resistance to reproductive tract infection by Candida albicans, associated with decreased responses of IL-17-dependent neutrophils. These findings emphasise tissue-specific complexities of different mucosal gamma delta cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.