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  • Review Article
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Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge

Abstract

T cell lineages are defined by specialized functions and differential expression of surface antigens, cytokines and transcription factors. Conventional CD4+ and CD8+ T cells are the best studied of the T cell subsets, but ‘unconventional’ T cells have emerged as being more abundant and influential than has previously been appreciated. Key subsets of unconventional T cells include natural killer T (NKT) cells, mucosal-associated invariant T (MAIT) cells and γδ T cells; collectively, these make up ~10% of circulating T cells, and often they are the majority of T cells in tissues such as the liver and gut mucosa. Defects and deficiencies in unconventional T cells are associated with autoimmunity, chronic inflammation and cancer, so it is important to understand how their development is regulated. In this Review, we describe the thymic development of NKT cells, MAIT cells and γδ T cells and highlight some of the key differences between conventional and unconventional T cell development.

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Fig. 1: Unconventional T cell populations in mice and humans.
Fig. 2: NKT cell development.
Fig. 3: MAIT cell development.
Fig. 4: Thymic γδ T cell development.

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Acknowledgements

D.G.P. is supported by a CSL Centenary Fellowship and by National Health and Medical Research Council of Australia (NHMRC) project grants (1145373,1140126 and 1122890). H.-F.K. is supported by an NHMRC ECF Fellowship (1160333), and S.P.B. is supported by a Dorevitch Cancer Research Fellowship.

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Pellicci, D.G., Koay, HF. & Berzins, S.P. Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge. Nat Rev Immunol 20, 756–770 (2020). https://doi.org/10.1038/s41577-020-0345-y

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