title: CD4+ T cell-mediated rejection of major histocompatibility complex class I-disparate grafts: a role for alloantibody.
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.
authors.affiliation: University Department of Surgery, Western Infirmary, Glasgow, Scotland.
authors.forename: A L
authors.initials: AL
authors.lastname: Morton
authors.forename: E B
authors.initials: EB
authors.lastname: Bell
authors.forename: E M
authors.initials: EM
authors.lastname: Bolton
authors.forename: H E
authors.initials: HE
authors.lastname: Marshall
authors.forename: C
authors.initials: C
authors.lastname: Roadknight
authors.forename: M
authors.initials: M
authors.lastname: McDonagh
authors.forename: J A
authors.initials: JA
authors.lastname: Bradley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D006084:Graft Rejection; D016027:Heart Transplantation; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007518:Isoantibodies / Q000276:immunology*; D051381:Rats; D016038:Skin Transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies