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Different Qualitative and Quantitative Regulation of V TCR Transcripts During Early Acute Allograft Rejection and Tolerance Induction¹

Marina Guillet^*, Sophie Brouard^*, Katia Gagne^*, Fabien Sébille^*, Maria-Cristina Cuturi^*, Marc-André Delsuc and Jean-Paul Soulillou^2,*

^* Institut National de la Santé et de la Recherche Médical, Unité 437, Centre Hospitalier Universitaire Hôtel-Dieu, Nantes, France; and Center de Biochimie Structurale, Faculté de Pharmacie, Montpellier, France

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 V mRNAs without exhibiting skewing of complementarity-determining region 3 (CDR3) length distribution. In this report, using this approach, we show in vivo that V 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 V 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.

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