[Characterization of tolerogen-producing cells and lymphoid tissues where self-tolerance is induced--a study on allogeneic bone marrow chimeras established with spontaneous leukemia prone mice].
SL/Kh strain of mice provides a spontaneous pre-B cell leukemia model and AKR/J mice provides a spontaneous thymoma model. Using these leukemia-prone mice, protective influence of bone marrow (BM) transplantation and tolerance induction to a host antigen, Mls-1a, after BM reconstitution were studied. When SL/Kh mice were reconstituted with BM cells from allogeneic C57BL/6 mice, these [B6-->SL] chimeric mice survived longer than non-treated SL or [SL-->SL] syngeneic chimeras. These findings are compatible to those obtained with [B6-->AKR] chimeras. In [D2-->SL] and [D2-->AKR] chimeras, V beta 6+ T cells reactive to Mls-1a had been clonally eliminated 5 weeks after BM reconstitution. On the other hand, minor graft versus host reaction (GVHR) abrogated the clonal elimination of V beta 6+ T cells in both [D2-->SL] and [D2-->AKR] chimeras. This abrogation appeared to be attributable to 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), although other T cell subsets also induced MLR under certain conditions. Administration of the CD8+CD44+ T cells from (AKR x BR)F1 mice induced clonal elimination of V beta 6+ T cells in the thymus and lymph nodes of [BR-->BR] syngeneic chimeras. By contrast, CD8+CD44- T cells induced partial reduction of V beta 6+ T cells only in lymph nodes. CD4+ T cells of Mls-1a type showed no tolerogenicity in this in vivo study, although these CD4+ T cells as well as CD8+ T cells evoked potentially MLR against Mls-1a. The present findings indicate that host CD8+CD44+ T cells are a major source of Mls-1a production in [Mls-1b-->Mls-1a] BM chimera system and suggest that CD44 expression on T cells is associated not only with high Mls-1a production but also with lymphoid tissues where the tolerogenic cells migrate.
Mishima
M
M
Section of Pathology, Hokkaido University, Sapporo, Japan.
D000818:Animals; D016026:Bone Marrow Transplantation; D002678:Chimera; D004195:Disease Models, Animal; D006087:Graft vs Host Reaction; D018960:Hyaluronan Receptors; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000378:metabolism*; D015448:Leukemia, B-Cell / Q000517:prevention & control*; D051379:Mice; D008806:Mice, Inbred AKR; D009930:Organic Chemicals; D010641:Phenotype; D018089:Superantigens; D014184:Transplantation, Homologous
D018960:Hyaluronan Receptors; D007166:Immunosuppressive Agents; D009930:Organic Chemicals; D018089:Superantigens; C029248:Tolerogen