Thursday, November 15, 2007

T cell maintenance: Care and Feeding

An abstract with the words ‘dynamic’ and ‘interplay’ usually signals a paper to be avoided but this one tells an interesting story about T cell survival. T cells require occasional stimulation through their antigen receptor (TCR) and feeding with interleukin-7 (IL-7), a product of stromal cells, monocytes, and some epithelial cells. T cells seem to share a limited amount of IL-7 through a negative feedback on the receptor gene transcription (IL-7Ra).

Tickling the TCR is trickier: too much could provoke autoimmunity, too little and the T cell dies. Here, Park and colleagues show that IL-7 (and other gamma common chain agonists) also regulates transcription of the CD8 gene encoding the monomorphic co-receptor of the TCR on a large subset of T cells. Moreover, they report that TCR signals from endogenous antigens inhibit CD8 expression, thereby promoting self tolerance.
The balance is illustrated in HY RAG mice, which are are engineered to contain only T cells specific for HY (a tissue antigen encoded on the Y-chromosome and therefore expressed only in males). If no antigen is present (females), then there is no TCR engagement, leading to more CD8 expression and less IL-7Ra expression than normal (Figure, top vs. second line). With more (and more) TCR engagement in males with appropriate H-2b alleles, comes less CD8 and more IL-7Ra expression (bottom 2 lines). They term this dynamic interplay “coreceptor tuning”.
Park JH, et al. Nat Immunol. 2007 Oct;8(10):1049-59. 'Coreceptor tuning': cytokine signals transcriptionally tailor CD8 coreceptor expression to the self-specificity of the TCR.