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Graft, Vol. 5, No. 7, 383-389 (2002)
DOI: 10.1177/152216202237625
© 2002 SAGE Publications

Antigen Receptor Revision as a Mechanism of Peripheral T Cell Tolerance

Cristine J. Cooper

Pamela J. Fink

Tolerance induction among mature T cells in the lymphoid periphery operates throughmany mechanisms, including the induction of anergy and cell death. By a newly de-scribedpathway, CD4+T cells that encounter a tolerogen are either deleted or are drivento reexpress the proteins that mediate DNA recombination and to rearrange and ex-pressdiverse novel antigen receptor genes encoding proteins that no longer recognizethe tolerogen. T cells that have successfully completed such receptor revision are bothfunctional and self-tolerant. The broad antigen receptor repertoire that results from receptorrevision benefits the individual faced with decreasing CD4+T cell counts due toelimination of T cells recognizing a widespread self-antigen that cannot be cleared.However, reexpression of the recombinase machinery in mature peripheral T cells offersthe potential for illegitimate recombination and subsequent dysregulation of cellularfunctions. Why would such a risky venture be undertaken? Perhaps the down-regulationof receptor expression that precedes revision decreases the basal level of signalingthrough the receptor, signaling that is critical for T cell survival. The cell may interpretthis loss of signaling capacity as a developing thymocyte would, by generating alternateantigen receptors whose expression levels are conducive to cell survival. In this way, receptorrevision may recapitulate thymocyte maturation.

Key Words: T cell receptor • major histocompatibility complex • recombination activating gene • transgenic • mammary tumor virus • green fluorescent protein • germinal center

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M. Ali, M. Weinreich, S. Balcaitis, C. J. Cooper, and P. J. Fink
Differential Regulation of Peripheral CD4+ T Cell Tolerance Induced by Deletion and TCR Revision
J. Immunol., December 1, 2003; 171(11): 6290 - 6296.
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