Abstract
Our understanding of T cell memory responses changed drastically with the discovery that specialized T cell memory populations reside within peripheral tissues at key pathogen entry sites. These tissue-resident memory T (TRM) cells can respond promptly to an infection without the need for migration, proliferation or differentiation. This rapid and local deployment of effector functions maximizes the ability of TRM cells to eliminate pathogens. TRM cells do not circulate through peripheral tissues but instead form isolated populations in the skin, gut, liver, kidneys, the reproductive tract and other organs. This long-term retention in the periphery might allow TRM cells to fully adapt to the local conditions of their environment and mount customized responses to counter infection and tumour growth in a tissue-specific manner. In the urogenital tract, TRM cells must adapt to a unique microenvironment to confer protection against potential threats, including cancer and infection, while preventing the onset of auto-inflammatory disease. In this Review, we discuss insights into the diversification of TRM cells from other memory T cell lineages, the adaptations of TRM cells to their local environment, and their enhanced capacity to counter infection and tumour growth compared with other memory T cell populations, especially in the urogenital tract.
Key points
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Memory T cells that reside in epithelial and mucosal tissues, and that possess superior protective capacities against infection compared with circulating memory T cells have been defined as tissue-resident memory T (TRM) cells.
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Pathogen-specific TRM cells are present in urogenital tract tissues, including the reproductive tract, bladder and kidney, where they make essential contributions to protection against pathogens.
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TRM cells also reside in carcinomas of the urogenital tract, where they counter tumour growth; however, their antitumour responses are inhibited by the engagement of inhibitory receptors, including programmed cell death protein 1.
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The pro-inflammatory activities of TRM cells might have harmful consequences in host tissues as is evidenced by their pathogenic role in the kidneys of patients with autoimmune disorders such as systemic lupus erythematosus, or their contribution to rejection in kidney transplant recipients.
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Acknowledgements
L.P.V. and K.P.J.M.vG. were supported by an LSBR Fellowship (# 1629) of The Landsteiner Foundation for Blood Transfusion Research, M.C.vA. was supported by The Dutch Kidney Foundation (# 18OKG22) and R.S. was supported by a Veni Fellowship (# 016.186.116) of The Dutch Research Council.
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Glossary
- Tertiary lymphoid structures
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Organized aggregates of B and T lymphocytes that develop in peripheral tissues in response to infection, inflammation or cancer.
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Parga-Vidal, L., van Aalderen, M.C., Stark, R. et al. Tissue-resident memory T cells in the urogenital tract. Nat Rev Nephrol 18, 209–223 (2022). https://doi.org/10.1038/s41581-021-00525-0
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DOI: https://doi.org/10.1038/s41581-021-00525-0
