Contribution of Host Radioresistant T Cells to the Clonal Elimination of Minor Lymphocyte Stimulatory-1a Reactive T Cells in Mouse Bone Marrow Chimeras

When bone marrow (BM) cells from I-E+ and minor lymphocyte stimulatory (Mls) antigen (Ag) disparate mice (Mls-1b) were transplanted to lethally irradiated Mls-1a reactive, Mls-1a reactive T cells were found to be completely deleted from the developing thymocyte population in these [Mls-1b→Mls-1a] radiation chimeras. It has been shown that BM-derived class II (Ia) positive cells play an essential role in this clonal deletion. Thus, Mls-1a Ag appeared to have been transferred from recipient cells to the Ia+ cells derived from donor BM. These Mls-1a-Ia complexes appear to be responsible for elimination of the Mls-1a reactive T cells that have also been derived from donor BM. However, definition of the cells of the recipient that generate the Mls-1a Ag and transfer them to the BM-derived Ia+ cells has remained unclear to date. In the analysis described herein, we have investigated the tolerogenicity of Mls-1a Ag derived from host T cells which represent a major population of radioresistant cells in the [Mls-1b→Mls-1a] chimeras. When recipient T cells that had been collected and purified from spleens of [Mls-1b→Mls-1a] chimeras were administered iv into [Mls-1b→Mls-1b] chimeras, Mls-1a reactive Vβ6+, Vβ8.1+, or Vβ9+ T cells were completely eliminated. Thus, residual radioresistant host T cells present in the radiation BM chimeras are the cells which produce the Mls-1a Ag. These Mls-1a Ags ultimately contribute to the clonal elimination of Mls-1a reactive T cells from the developing thymocyte population. The present findings indicate that recipient T cells which can survive lethal irradiation and produce intrinsic superantigens alter eventually the T cell repertoire in the thymus which have been developing from precursors of donor BM.