CD4-CELL-MEDIATED REJECTION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-DISPARATE GRAFTS - A ROLE FOR ALLOANTIBODY( T)

Experimental studies of the T cell requirement for rejection of class I major histocompatibility complex (MHC)-disparate grafts have generat ed controversy over both the autonomy of CD8+ T cells and the mechanis m whereby CD4+ T cells are able to independently mediate rejection. In this study of rejection of RT1A(a) class I MHC-disparate rat cardiac and skin allografts by high-responder PVG RT1u recipients. we show tha t elimination of CD8+ T cells [by anti-CD8 monoclonal antibody (mAb) a dministration 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 r econstituted with CD8+ T cells failed to reject class I-disparate skin grafts for several weeks and eventual rejection correlated with re-em ergence of a small number of donor derived CD4+ T cells. Conversely, a nti-CD8-treated nude rats reconstituted with CD4+ T cells alone rapidl y rejected class I-disparate skin grafts. Passive transfer of anti-cla ss I immune serum to anti-CD4-treated euthymic recipients promptly res tored their ability to specifically reject a class I-disparate heart g raft. Similarly, passive transfer of immune serum to PVG-RT1u nude rat s bearing skin allografts caused destruction of class I-disparate but not third-party grafts. These results demonstrate that CD4+ T cells ar e both necessary and sufficient to cause rejection of class I-disparat e heart and skin grafts in this model and that CD4+ T cell-dependent a lloantibody plays a decisive role in effecting rejection.