Abstract
This most comprehensive analysis to date of γδ 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 Vγ6Vδ1 TCR, and produced interleukin (IL)-17A upon stimulation. Nonetheless, contrasting with earlier reports, uterine γδ T cells were not obviously intraepithelial, being more akin to sub-epithelial Vγ6Vδ1+ T cells at several other anatomical sites. By contrast to other tissues however, the uterine compartment also included non-Vγ6+, IFN-γ-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, γδ 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 γδ cell compartments, and their evident importance in lymphoid stress-surveillance against barrier infection.
Highlights
Many tissues harbour two categories of lymphocytes which are largely noncirculating.[1]
We have focused on the murine female reproductive tract (FRT)
Unlike the case for dendritic epidermal T cells (DETC), the representation of γδ T cells in the uterus overtly decreased in older mice, and by weeks 12–16 comprised
Summary
Many tissues harbour two categories of lymphocytes which are largely noncirculating.[1] The first category includes tissue-resident memory T (TRM) cells that enter tissues following priming in lymphoid organs and compose reservoirs of cells responsive to local reinfection and/or tumour challenge.[1] TRM have been well-studied in skin, lung, and reproductive tissues.[1]. The second category comprises cells that home to the target organ developmentally, without requiring lymphoid priming.[2] In mice, such lymphocytes include large subsets of γδ T cells with restricted TCR repertoires that have been well-studied in the gut and epidermis. Clear counterparts of these cells were recently identified in human gut.[3]
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