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T CELL DEVELOPMENT

Signal length not strength guides T cell fate

Nature Reviews Immunology volume 22, page 407 (2022)Cite this article

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During positive selection in the thymus, double-positive (DP) thymocytes expressing both CD4 and CD8 coreceptors develop into either MHC class II-restricted CD4+ T cells with helper function or MHC class I-restricted CD8+ T cells with cytotoxic function, but it has been unclear how coreceptor expression and T cell function are coordinated. T cell receptor (TCR) ‘signal strength’ models propose that strong signals through CD4–TCR induce a helper-lineage fate, whereas weak signals through CD8–TCR induce a cytotoxic lineage fate. ‘Kinetic signalling’ models propose that longer-duration CD4–TCR signals versus shorter-duration CD8–TCR signals determine helper versus cytotoxic fates. Shinzawa et al. now report the generation of FlipFlop mice, in which the coreceptor proteins encoded by the Cd4 and Cd8 loci are reversed, shedding light on the importance of TCR signal length versus strength in T cell lineage fate.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Kirsty Minton

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  1. Kirsty Minton
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Correspondence to Kirsty Minton.

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Minton, K. Signal length not strength guides T cell fate. Nat Rev Immunol 22, 407 (2022). https://doi.org/10.1038/s41577-022-00736-x

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