Tolerogen-Producing Cells in Allogeneic Bone Marrow Chimeras Established with Spontaneously Leukemia-Prone Mice

Using SL/Kh mice and AKR/J mice, which are animal models for spontaneous pre-B-cell leukemia and thymic lymphoma, respectively, we studied the protective influence of allogeneic bone marrow transplantation (BMT) and the induction of tolerance to Mls-1a, a host antigen. When BM cells from allogeneic C57BL/6 mice were used to reconstitute self-tolerance SL/Kh mice, these [B6→SL] chimeric mice survived for a longer time than non-treated SL or [SL→SL] syngeneic chimeras. These findings are compatible with results previously obtained for [B6→AKR] chimeras. In [B10. D2→SL] and [B10. D2→AKR] chimeras, Vβ6+ T-cells reactive to Mls-1a were eliminated 5 weeks after BMT. On the other hand, minor graft versus host reaction (GVHR) abrogated the clonal elimination of Vβ6+ T-cells in both [B10. D2→SL] and [B10. D2→AKR] chimeras. The cause of this abrogation was attributed to the early disappearance of Mls-1a-producing host T-cells in the GVHR chimeras. The cells responsible for the Mls-1a production were revealed to be mainly CD8+ CD44+ T-cells, by in vitro mixed lymphocyte reaction (MLR) and in vivo tolerance induction. The present findings indicate that host CD8+ CD44+ T-cells constitute the major source of Mls-1a antigens in the [Mls-1b→Mls-1a] BM chimera system.