Bone marrow-derived cells are essential for intrathymic deletion of self-reactive T cells in both the host- and donor-derived thymocytes of fully allogeneic bone marrow chimeras.
The fate of self-reactive T cells was examined in both the host- and donor-derived thymocytes of fully allogeneic bone marrow (BM) chimeras of two strain combinations of AKR/J (H-2k, IE+, Thy-1.1, Mls-1a2b) and C57BL/6 (H-2b, IE-, Thy-1.2, Mls-1b2b). Sequential appearance of host- and donor-derived T cells occurred in the thymus of both AKR----B6 and B6----AKR chimeras in which 5 x 10(6) of T cell-depleted BM cells were used to reconstitute recipients lethally irradiated with 950 rad. Thymocytes bearing V beta 6 high, which recognize MHC class II IE-binding Ag encoded by Mls-1a allele, were detected in neither host- nor donor-derived thymocytes of AKR-B6 chimeras in which Mls-1a and IE were expressed only by the BM-derived cells. Thymocytes bearing V beta 11high capable of recognizing IE were also deleted in the host- and donor-derived thymocytes of the AKR----B6 chimeras. One million of BM cells were inadequate to deletion of the B beta 6high and V beta 11high T cells in the host-derived thymocytes of these chimeras. On the other hand, significant number of V beta 6high and V beta 11high thymocytes were detected in both the host- and donor-derived thymocytes in B6----AKR chimeras where sufficient dose of IE- stem cells were used to reconstitute irradiated Mls-1aIE+ recipients. These results suggest that clonal deletion of the host- and donor-reactive T cells in both the host- and donor-derived thymocytes is an important mechanism for the induction of transplantation tolerance in allogeneic BM chimeras and that BM-derived APC may be essential for the intrathymic elimination of both the host- and donor-reactive T cells in the BM chimeras.
Yoshikai
Y
Y
Department of Immunology, Kyushu University, Fukuoka, Japan.
Ogimoto
M
M
Matsuzaki
G
G
Nomoto
K
K
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000032:analysis; D001324:Autoantigens / Q000276:immunology; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens; D002678:Chimera; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D008912:Minor Histocompatibility Loci; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D001324:Autoantigens; D015704:CD4 Antigens; D016827:CD8 Antigens; D000949:Histocompatibility Antigens Class II; C024138:I-E-antigen