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Tolerance induction among mature T cells in the lymphoid periphery operates through many mechanisms, including the induction of anergy and cell death. By one newly described pathway, CD4+ T cells that encounter a tolerogen are either deleted or are driven to reexpress the proteins that mediate DNA recombination and to rearrange and express diverse novel antigen receptor genes encoding proteins that no longer recognize the tolerogen. T cells that have successfully completed such receptor revision are both functional and self tolerant.

The broad antigen receptor repertoire that results from receptor revision benefits the individual faced with decreasing CD4+ T cell counts due to elimination of T cells recognizing a wide-spread self antigen that cannot be cleared. However, reexpression of the recombinase machinery in mature peripheral T cells offers the potential for illegitimate recombination and subsequent dysregulation of cellular functions. Why would such a risky venture be undertaken? Perhaps the downregulation of receptor expression that precedes revision decreases the basal level of signaling through the receptor, signaling that is critical for T cell survival. The cell may interpret this loss of signaling capacity as a developing thymocyte would, by generating alternate antigen receptors whose expression levels are conducive to cell survival. In this way, receptor revision may recapitulate thymocyte maturation.

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