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 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Animals
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Animals, Congenic
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Blood Transfusion / statistics & numerical data
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Complementarity Determining Regions / analysis
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Complementarity Determining Regions / biosynthesis*
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Complementarity Determining Regions / genetics
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Down-Regulation / genetics
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Down-Regulation / immunology
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
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Graft Rejection / genetics
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Graft Rejection / immunology*
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Heart Transplantation / immunology
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Heart Transplantation / statistics & numerical data
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Histocompatibility Testing / statistics & numerical data
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Immune Tolerance* / genetics
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Interphase / genetics
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Interphase / immunology
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Male
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Multigene Family / immunology
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Normal Distribution
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RNA, Messenger / analysis
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RNA, Messenger / biosynthesis
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Rats
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Rats, Inbred Lew
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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Transcription, Genetic / immunology*
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Transplantation, Homologous / statistics & numerical data
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Complementarity Determining Regions
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RNA, Messenger