title: Clonal deletion of self-reactive T cells in irradiation bone marrow chimeras and neonatally tolerant mice. Evidence for intercellular transfer of Mlsa.
abstract: Tolerance to Mlsa has been shown to be associated with clonal deletion of cells carrying TCR beta chain variable regions V beta 6 or V beta 8.1 in mice possessing I-E antigens. To evaluate the rules of tolerance induction to Mlsa we prepared irradiation bone marrow chimeras expressing Mlsa or Mlsb and I-E by different cell types. Deletion of V beta 6+, Mlsa-reactive T cells required the presence of Mlsa and I-E products either on bone marrow-derived cells or on irradiated recipient cells. Tolerance was induced when Mlsa and I-E were expressed by distinct cells of the chimera. Also neonatally tolerized mice exhibited depletion of V beta 6+ cells after injection of I-E- Mlsa spleen cells (DBA/1) into newborn I-E+ Mlsb mice (BALB/c x B10.G)F1. These results suggest that the product of the Mlsa locus is soluble and/or may be transferred from cell to cell and bound to I-E antigens. The chimera experiments also showed that tolerance to Mlsa is H-2 allele independent, i.e., is apparently unrestricted. Differentiation of chimeric (H-2d/Mlsa x H-2q/Mlsb)F1 stem cells in either an H-2d or an H-2q thymus revealed that tolerance assessed by absence of V beta 6+ T cells is not dependent on the thymically determined restriction specificity of T cells.
authors.affiliation: Institute of Pathology, University Hospital, Zürich, Switzerland.
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: R
authors.initials: R
authors.lastname: Schneider
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: H R
authors.initials: HR
authors.lastname: MacDonald
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007108:Immune Tolerance; D051379:Mice; D008815:Mice, Inbred Strains; D011828:Radiation Chimera; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001324:Autoantigens; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta