Clonal deletion and clonal anergy in allogeneic bone marrow chimeras prepared with TBI or TLI

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Abstract
The evolution of Vβ6 ‐ expressing C3H (Hk2, 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 (Hk2, Thy 1.1, MIS a +) cells. After TBI (9.5 Gy) all Vβ6+ Thy 1.2 (C3H) cells, which are capable of reacting against the MIS 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 times 106 T‐cell‐depleted (TCD) AKR BM cells. When, in the opposite combination, 30 times 106 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 Vβ6+ C3H cells. After injection of 30 times 106 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 Vβ6+ cells were only partially deleted and anergized as they did not respond in vitro after stimulation with Mls a + AKR cells or anti‐Vβ6 mAb. Cells suppressing anti‐Mls a‐reacting C3H cells were not found. After injection of 15 times 106 AKR cells more C3H cells were found in the thymus, but only a minority of Vβ6+ 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.