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

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.

Microbiota-dependent expansion of testicular IL-17-producing Vγ6+ γδ T cells upon puberty promotes local tissue immune surveillance

“…Along the same line, recent findings have reported a protective role for Vγ6 + γδ T cells against Candida albicans in the female reproductive tract. 39 Together, these examples may serve as a proof of concept for an antimicrobial immune surveillance of mucosal γδ17 cells in the male and female reproductive organs, predicting a similar response to other pathogens, such as Escherichia coli (E. coli) or Chlamydia, although further investigation will be needed to test this hypothesis.…”

“…Over the past few years, tissue-resident γδ T cells have been explored in many specific tissues, such as the skin, 35 lung, 36 gingiva, 29 eye, 37 trachea 38 and brain meninges, 21 and also in the female sexual organs such as the uterus and vagina. 8,10,39 Therefore, it is not surprising that γδ T cells are also present in the male reproductive organs. Unexpectedly, γδ T cells accounted for almost 50% of all lymphocytes in "immune privileged" testis.…”

Gut γδ T cells as guardians, disruptors, and instigators of cancer

“…16 Vγ6 cells also express a semi-invariant TCR, 17,18 and these cells localize primarily to reproductive organs, tongue, and lung. [19][20][21] In adult mice, Vγ5 and Vγ6 cells (and some IL-17-producing Vγ4 cells in the colon) no longer require the thymus for development. They exist mostly as self-generating, tissue-resident cells.…”

Recognition of Candida albicans and Role of Innate Type 17 Immunity in Oral Candidiasis

“…γδ T cells can produce high amounts of IL-17 on a per-cell basis [119,120], and thus are potentially an important source of oral IL-17, which plays a crucial role in OPC [30,114]. Interestingly, the development of uterine γδ T cells in mice was independent from microflora, while Vγ6+ γδT cells in the gingiva were shown to be dependent [114,121]. Notably, this salient feature of gingival γδT cells appeared to have a subset-dependency since Vγ4+ γδT cells were unaffected.…”

“…Therefore, γδT cells activity depends on many factors, such as host and tissue specificity, and immune environment, which implicates complex interplay between C. albicans and its host. For instance, deficiency of Vγ6+ γδ T cells was shown to impair recruitment of neutrophils in mice reproductive tract, which severely impaired resistance to C. albicans [121]. Kidney-resident γδT cells with a 6-to 7-fold increase were shown to be the primary source of IL-17 during disseminated C. albicans infection [122].…”