Clonal deletion and clonal anergy in allogeneic bone marrow chimeras prepared with TBI or TLI.
The evolution of Vbeta6-expressing C3H (H2k, Thy 1.2, Mls a-) lymphocytes was investigated in C3H recipients mice pretreated with total body irradiation (TBI) or total lymphoid irradiation (TLI) and infusion of AKR (H2k, Thy 1.1, Mls a+) cells. After TBI (9.5 Gy) all Vbeta6+ Thy 1.2 (C3H) cells, which are capable of reacting against the Mls a antigen that like expressed by AKR mice, were deleted in the thymus and the periphery in stable bone marrow (BM) chimeras obtained by infusion of 5 x 10(6) T-cell-depleted (TCD) AKR BM cells. When, in the opposite combination, 30 x 10(6) C3H spleen cells were infused into TBI-treated AKR cells, all animals developed graft-versus-host disease (GVHD) with no clonal deletion and in contrast, showed an increase in Vbeta6+ C3H cells. After injection of 30 x 10(6) AKR BM cells into TLI-treated C3H mice no C3H cells were detected in the thymus and only a small percentage in the periphery. Within these C3H cells Vbeta6+ cells were only partially deleted and anergized as they did not respond in vitro after stimulation with Mls a+ AKR cells or anti-Vbeta6 mAb. Cells suppressing anti-Mls a-reacting C3H cells were not found. After injection of 15 x 10(6) AKR cells more C3H cells were found in the thymus, but only a minority of Vbeta6+ cells persisted in the periphery of these animals. In conclusion in TBI-prepared chimeras only clonal deletion occurred, whereas in TLI-prepared chimeras both clonal deletion and anergy occurred in maintaining tolerance.
Transplantation Laboratory, Rega Institute, Leuven, Belgium.
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A
Salam
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M
Vandeputte
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M
Waer
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D017635:Clonal Anergy / Q000276:immunology*; D017637:Clonal Deletion / Q000276:immunology*; D006085:Graft Survival / Q000276:immunology*; D007165:Immunosuppression Therapy / Q000379:methods*; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000528:radiation effects; D051379:Mice; D008806:Mice, Inbred AKR; D008809:Mice, Inbred C3H; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology; D013997:Time Factors; D018183:Transplantation Chimera / Q000276:immunology*; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation