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

Mucosal Immunol. 2020 Nov;13(6):969-981. doi: 10.1038/s41385-020-0305-7. Epub 2020 May 29.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Candida albicans / physiology*
  • Candidiasis / immunology*
  • Disease Resistance
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neutrophils / immunology*
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • T-Lymphocytes / immunology*
  • Uterus / immunology*
  • Vagina / immunology*
  • Vagina / microbiology

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Interferon-gamma