The immune system is charged with the dual tasks of defense against invading pathogens and preservation of self. For T cells, carrying out these simultaneous


Although intrathymic negative selection operates primarily to eliminate overtly self-reactive thymocytes, the induction of tolerance among mature peripheral T cells operates through many pathways.

Through the process of TCR revision, mature peripheral CD4+ T cells can be driven to reinitiate DNA rearrangement within the TCR loci and express diverse, newly generated, nonautoreactive TCRs.

The decision to upregulate RAG expression and undergo TCR revision may be a byproduct of T cell maturation.

The surprisingly broad TCR repertoire that results from TCR revision is an obvious benefit to the individual faced with decreasing CD4+ T cell counts due to elimination of cells recognizing a self antigen it is unable to clear.

Reexpression of the recombinase machinery in mature peripheral T cells offers the potential for aberrant juxtaposition of cellular oncogenes and lymphocyte-specific promoters.

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