The mechanisms that integrate the signals delivered through the TCR and cytokine receptors for the differentiation and proliferation of T cells are incompletely understood. In Immunity, Hodes and colleagues show that the transcriptional regulator p53 is needed to integrate IL-2-induced proliferation in the context of an antigen-specific response in both naive CD4+ T cells and memory CD4+ T cells. While wild-type CD4+ T cells require signaling from both the TCR and IL-2 for proliferation, p53-deficient CD4+ T cells undergo abundant proliferation in response to IL-2 alone. Stimulation of T cells with IL-2 in the absence of TCR signaling induces sustained p53 expression, while costimulation via the TCR terminates the initial increase in p53 protein via a decrease in p53 mRNA and induction of the ubiquitination and proteosomal degradation of p53 mediated by the E3 ubiquitin ligase Mdm2. Downregulation of p53 is required for TCR-induced proliferation, which suggests a central role for p53 in controlling antigen-specific CD4+ T cell responses.
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Visan, I. Specificity control. Nat Immunol 15, 601 (2014). https://doi.org/10.1038/ni.2934
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DOI: https://doi.org/10.1038/ni.2934