Revision Targets Mature Peripheral T Cells

Several observations indicate that TCR revision is a peripheral event targeting mature T cells. Vpendo+Vp5-CD4+ T cells, the products of TCR revision, appear with similar kinetics in both thymectomized and unmanipulated Mtv-8+ Vp5 Tg mice.25 Conversely, Vpendo+Vp5-CD4+ thymocytes cannot be detected in mice at any age, although the diversity of the expressed endogenous TCR repertoire and the minimal mouse-to-mouse variation in this diversity together suggest their generation is not a rare event.21 Sequence analyses of revised TCR-p chain genes indicate they contain regions of nontemplated nucleotides that are atypical of those generated in the adult thymus.21 Most definitively, GFP Tg Vp5 Tg mice that have been thymectomized more than 4 weeks previously can generate GFP+Vpendo+Vp5-CD4+ T cells, and these cells are acutely activated and RAG-expressing (our unpublished observations). Together, these results indicate that through the process of TCR revision, mature peripheral CD4+ T cells can be driven to reinitiate recombination within the TCR loci and express newly generated, nonautoreactive TCRs.

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