CONTRIBUTION OF HOST RADIORESISTANT T-CELLS TO THE CLONAL ELIMINATION OF MINOR LYMPHOCYTE STIMULATORY-1(A) 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-1(b)) were transplanted to lethally irradiated Mls-1(a) mice, Mis-1(a) reactive T cells were found to be completely deleted from the developing thymocyte population in these [Mls-1(b)-->Mls-1(a)] radiation chimeras. It has been shown that BM-derived class II (Ia) positive cells play an essential role in this clonal deletion. Thus, Mls-la Ag appeared to have been transferred from recipient cells to the Ia(+) cells derived from donor BM. These Mls-1(a)-Ia complexes appear to be responsible for elimination of the Mls-1(a) reactive T cells that have also been derived from donor BM. However, definition of the cells of the recipient that generate the Mls-1(a) 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-1(a) Ag derived from host T cells which represent a major population of radioresistant cells in the [Mls-1(b)-->Mls-1(a)] chimeras. When recipient T cells that had been collected and purified from spleens of[Mls-1(b)-->Mls-1(a)] chimeras were administered iv into [Mls-1(b)-->Mls-1(b)] chimeras, Mls-1(a) reactive V beta 6(+), V beta 8.1(+), or V beta 9(+) T cells were completely eliminated. Thus, residual radioresistant host T cells present in the radiation BM chimeras are the cells which produce the Mls-1(a) Ag. These Mls-1(a) Ags ultimately contribute to the clonal elimination of Mls-1(a) 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 after eventually the T cell repertoire in the thymus which have been developing from precursors of donor BM. (C) 1994 Academic Press, Inc.