This study examines the molecular programmes that determine the proliferative defect of self-reactive CD8+ T cells in response to antigen; this defect is a component of peripheral tolerance. Using a T cell receptor-transgenic mouse model, the authors showed that self-reactive tolerant T cells can respond to immunization with their cognate antigen during homeostatic proliferation in lymphopenic recipients, but that these 'rescued' T cells reacquire tolerance once the hosts are lymphoreplete, even in the absence of the self antigen ('re-tolerized' T cells). Microarray analysis showed that tolerant T cells have a specific gene-expression signature, which was largely replaced by a gene signature similar to that of memory T cells in rescued T cells. Re-tolerized T cells re-established the gene signature of tolerant T cells, and the authors identified microRNA-181a as a possible key regulator of a genetic memory of tolerance.
ORIGINAL RESEARCH PAPER
Schietinger, A. et al. Rescued tolerant CD8 T cells are preprogrammed to reestablish the tolerant state. Science 335, 723–727 (2012)Article
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Minton, K. Genetic regulation of peripheral tolerance. Nat Rev Immunol 12, 151 (2012). https://doi.org/10.1038/nri3182
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DOI: https://doi.org/10.1038/nri3182