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Rejection of cardiac allografts by T cells expressing a restricted repertoire of T‐cell receptor V β genes
Author(s) -
SHIRWAN H.,
BARWARI L.,
CRAMER D. V.
Publication year - 1997
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1997.00187.x
Subject(s) - repertoire , t cell receptor , major histocompatibility complex , biology , gene , t cell , beta (programming language) , transplantation , adoptive cell transfer , heart transplantation , microbiology and biotechnology , immunology , genetics , immune system , medicine , physics , acoustics , computer science , programming language
We have recently shown that T cells infiltrating cardiac allografts early in graft rejection use a limited T‐cell receptor (TCR) V β repertoire. In this study we tested whether this limited repertoire of V β genes is important for graft rejection. A cell line, AL2‐L3, was established from LEW lymphocytes infiltrating ACI heart allografts 2 days after transplantation. This cell line is composed of CD4 + T cells that primarily recognize the class II RT1.B major histocompatibility complex (MHC) molecule expressed by the donor graft. This cell line precipitated acute rejection of donor hearts with a median survival time (MST) of 10·5 days following adoptive transfer to sublethally irradiated LEW recipients. This rate of graft rejection was significantly ( P <0·0007) accelerated when compared with a MST of 60 days for allografts in irradiated control recipients. The AL2‐L3‐mediated acceleration of graft rejection was donor specific as WF third‐party heart allografts were rejected with a delayed tempo (MST=28·5 days). The V β repertoire of this cell line was primarily restricted to the expression of V β 4, 15 and 19 genes. The nucleotide sequence analysis of the β ‐chain cDNAs from this cell line demonstrated that the restricted use of the V gene repertoire was not shared with the N, D and J regions. A wide variety of CDR3 loops and J β genes were used in association with selected V β genes. These data provide evidence for the role a restricted repertoire of V β genes plays in cardiac allograft rejection in this model. The restricted usage of the V β repertoire in an early T‐cell response to allografts may provide the opportunity to therapeutically disrupt the rejection reaction by targeting selected T‐cell populations for elimination at the time of organ transplantation.