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[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].

Abstract
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.
AuthorsM Mishima
Journal[Hokkaido igaku zasshi] The Hokkaido journal of medical science (Hokkaido Igaku Zasshi) Vol. 70 Issue 6 Pg. 817-27 (Nov 1995) ISSN: 0367-6102 [Print] Japan
PMID8582705 (Publication Type: Journal Article)
Chemical References
  • Hyaluronan Receptors
  • Immunosuppressive Agents
  • Organic Chemicals
  • Superantigens
  • Tolerogen
Topics
  • Animals
  • Bone Marrow Transplantation
  • Chimera
  • Disease Models, Animal
  • Graft vs Host Reaction
  • Hyaluronan Receptors
  • Immune Tolerance
  • Immunosuppressive Agents (metabolism)
  • Leukemia, B-Cell (prevention & control)
  • Mice
  • Mice, Inbred AKR
  • Organic Chemicals
  • Phenotype
  • Superantigens
  • Transplantation, Homologous

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