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Nat Immunol. 2007 Oct;8(10):1049-59. Epub 2007 Sep 16.

'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.

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Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.


T cell immunity requires the long-term survival of T cells that are capable of recognizing self antigens but are not overtly autoreactive. How this balance is achieved remains incompletely understood. Here we identify a homeostatic mechanism that transcriptionally tailors CD8 coreceptor expression in individual CD8+ T cells to the self-specificity of their clonotypic T cell receptor (TCR). 'Coreceptor tuning' results from interplay between cytokine and TCR signals, such that signals from interleukin 7 and other common gamma-chain cytokines transcriptionally increase CD8 expression and thereby promote TCR engagement of self ligands, whereas TCR signals impair common gamma-chain cytokine signaling and thereby decrease CD8 expression. This dynamic interplay induces individual CD8+ T cells to express CD8 in quantities appropriate for the self-specificity of their TCR, promoting the engagement of self ligands, yet avoiding autoreactivity.

[Indexed for MEDLINE]

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