γδ T cells in tissue physiology and surveillance

Abstract

γδ T cells are a unique T cell subpopulation that are rare in secondary lymphoid organs but enriched in many peripheral tissues, such as the skin, intestines and lungs. By rapidly producing large amounts of cytokines, γδ T cells make key contributions to immune responses in these tissues. In addition to their immune surveillance activities, recent reports have unravelled exciting new roles for γδ T cells in steady-state tissue physiology, with functions ranging from the regulation of thermogenesis in adipose tissue to the control of neuronal synaptic plasticity in the central nervous system. Here, we review the roles of γδ T cells in tissue homeostasis and in surveillance of infection, aiming to illustrate their major impact on tissue integrity, tissue repair and immune protection.

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Fig. 1: Thymic developmental waves and tissue homing of γδ T cell subsets.
Fig. 2: γδ T cell homeostasis in tissues.
Fig. 3: Roles of γδ T cells in tissue physiology.
Fig. 4: γδ T cell functions in infected tissues.

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Acknowledgements

This Review is dedicated to the loving memory of the authors’ colleague and γδ T cell pioneer, W. Havran (1955–2020). The authors thank A. Hayday for inspiring discussions on these topics. Their work is supported by La Caixa Banking Foundation (project HR18-00069). J.C.R received a junior investigator contract from Fundação para a Ciência e Tecnologia (IF/00013/2014) and N.L. received an EMBO long-term fellowship (ALTF 752-2018).

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J.C.R., N.L. and B.S.-S. conceived and wrote the article.

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Correspondence to Julie C. Ribot or Bruno Silva-Santos.

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Glossary

Dendritic epidermal T cells

(DETCs). A common designation for the monoclonal Vγ5+ γδ T cell subset that resides in the murine epidermis and contributes to environmental sensing, wound healing and antitumour immunity.

Adaptate

A term initially proposed by Adrian Hayday to describe the blend of innate and adaptive immune features show by γδ T cells.

Ketogenic diet

A low-carbohydrate, high-fat diet that induces a metabolic state called ‘ketosis’.

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Ribot, J.C., Lopes, N. & Silva-Santos, B. γδ T cells in tissue physiology and surveillance. Nat Rev Immunol (2020). https://doi.org/10.1038/s41577-020-00452-4

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