THE ROLE OF HOST T CELL SUBSETS IN BONE MARROW REJECTION DIRECTED TO ISOLATED MAJOR HISTOCOMPATIBILITY COMPLEX CLASS I VERSUS CLASS II DIFFERENCES OF bm1 and bm12 MUTANT MICE1,2

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Abstract

An expanded pool of unrelated donors (URD) is now being utilized for clinical allogeneic bone marrow transplantation. Because URD transplants can involve a mismatch at least at one genotypic MHC locus, we developed a C57BL/6 congenic mouse model to better understand graft rejection based exclusively on MHC class I or class II disparities. T cell-depleted (TCD) BM from class II-disparate mutant bm 12 mice was transplanted into irradiated C57BL/6-Ly5.2 congenic hosts. These mice express a different allelic form of the Ly5 (CD45) marker than bm 12 and thus permit definitive typing of reconstituted mice by flow cytometry. Peripheral blood typing indicated that host-mediated graft rejection was restricted to class II-reactive CD4+ cells since an anti-CD4 monoclonal antibody significantly inhibited rejection by enhancing the level of mean donor cell engraftment from 13% to 53%. The administration of anti-CD8 had no inhibitory effect on the ability of the recipient to reject the donor graft. Hematologic reconstitution studies revealed that there was a direct relationship between the level of donor cell engraftment and the extent of lymphoid, myeloid, and erythroid recovery. Mice that did not engraft had sustained reductions in in hematologic recovery. In other studies, TCD BM from bm 1 mice mutated only in the MHC class I region was rejected by C57BL/6-Ly5.2 recipients. Anti-CD8 mAb in

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