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  • Title: CD4+ T cell-mediated rejection of major histocompatibility complex class I-disparate grafts: a role for alloantibody.
    Author: Morton AL, Bell EB, Bolton EM, Marshall HE, Roadknight C, McDonagh M, Bradley JA.
    Journal: Eur J Immunol; 1993 Sep; 23(9):2078-84. PubMed ID: 8103742.
    Abstract:
    Experimental studies of the T cell requirement for rejection of class I major histocompatibility complex (MHC)-disparate grafts have generated controversy over both the autonomy of CD8+ T cells and the mechanism whereby CD4+ T cells are able to independently mediate rejection. In this study of rejection of RT1Aa class I MHC-disparate rat cardiac and skin allografts by high-responder PVG RT1u recipients, we show that elimination of CD8+ T cells [by anti-CD8 monoclonal antibody (mAb) administration in vivo] fails to prolong graft survival, whereas partial depletion of CD4+ T cells (by anti-CD4 mAb treatment) markedly delays rejection of class I-disparate heart grafts, and marginally prolongs survival of skin grafts. Anti-CD4-treated PVG-RT1u athymic nude rats reconstituted with CD8+ T cells failed to reject class I-disparate skin grafts for several weeks and eventual rejection correlated with re-emergence of a small number of donor derived CD4+ T cells. Conversely, anti-CD8-treated nude rats reconstituted with CD4+ T cells alone rapidly rejected class I-disparate skin grafts. Passive transfer of anti-class I immune serum to anti-CD4-treated euthymic recipients promptly restored their ability to specifically reject a class I-disparate heart graft. Similarly, passive transfer of immune serum to PVG-RT1u nude rats bearing skin allografts caused destruction of class I-disparate but not third-party grafts. These results demonstrate that CD4+ T cells are both necessary and sufficient to cause rejection of class I-disparate heart and skin grafts in this model and that CD4+ T cell-dependent alloantibody plays a decisive role in effecting rejection.
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