Different qualitative and quantitative regulation of V beta TCR transcripts during early acute allograft rejection and tolerance induction.
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 Vbeta mRNAs without exhibiting skewing of complementarity-determining region 3 (CDR3) length distribution. In this report, using this approach, we show in vivo that Vbeta 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 Vbeta 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.
Guillet
Marina
M
Institut National de la Santé et de la Recherche Médical, Unité 437, Centre Hospitalier Universitaire Hôtel-Dieu, 30 boulevard Jean Monnet, 44093 Nantes Cedex 01, France.
Brouard
Sophie
S
Gagne
Katia
K
Sébille
Fabien
F
Cuturi
Maria-Cristina
MC
Delsuc
Marc-André
MA
Soulillou
Jean-Paul
JP
D000208:Acute Disease; D000818:Animals; D020296:Animals, Congenic; D001803:Blood Transfusion / Q000706:statistics & numerical data; D022801:Complementarity Determining Regions / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D016027:Heart Transplantation / Q000276:immunology / Q000706:statistics & numerical data; D006650:Histocompatibility Testing / Q000706:statistics & numerical data; D007108:Immune Tolerance / Q000235:genetics; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008297:Male; D005810:Multigene Family / Q000276:immunology; D016011:Normal Distribution; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology*; D014184:Transplantation, Homologous / Q000706:statistics & numerical data; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D022801:Complementarity Determining Regions; D012333:RNA, Messenger