Different Qualitative and Quantitative Regulation of Vβ TCR Transcripts During Early Acute Allograft Rejection and Tolerance Induction

Abstract

Recently, using a global method of T cell repertoire analysis, we showed that purified naive T cells confronted in vitro with allogeneic APCs in a direct pathway-restricted MLR up-regulate their Vβ mRNAs without exhibiting skewing of complementarity-determining region 3 (CDR3) length distribution. In this report, using this approach, we show in vivo that Vβ transcript regulation and CDR3 length distribution follow the same pattern during acute rejection of MHC-incompatible heart allografts. In contrast, in tolerance induction by priming of recipients with donor cells, the vigorous Vβ mRNA accumulation with Gaussian CDR3 length distribution is abolished, providing a possible explanation for the down-regulation of activated T cells in tolerant animals. In addition, tolerated grafts harbor T cells with a highly altered repertoire, suggestive of self-restricted presentation with some patterns corresponding to previously identified regulatory cells.