[A study on clonal elimination of auto-reactive thymocytes in bone marrow chimera mice].
Bone marrow (BM) chimera mice were established by injecting BM cells from B10 H-2 congenic or recombinant mice (Mls-1b) into lethally irradiated AKR (Mls-1a) mice in order to elucidate what type of cells were responsible for intrathymic clonal elimination of self-reactive V beta 6+T cells that are reactive to Mls-1a plus I-E products. When I-E+ mice were donors, V beta 6+ SP thymocytes were not eliminated. However, in chimeras where B10 (I-Ab, I-E-) or B10.A(4R)(I-Ak, I-E-) mice were donors, variable proportions of V beta 6+ SP cells were observed. These differences appeared to be attributable to the difference in affinity between class II antigens expressed on BM derived cells and Mls-1a on recipient cells. When AKR mice were reconstituted with BM cells from both B10 and AKR mice, V beta 6+ SP thymocytes were eliminated according to frequencies of the AKR derived cells. These findings collectively indicate that the BM derived thymic stromal cells are essential for the clonal elimination of V beta 6+ cells. However, in GVHR chimeras prepared by injecting of both BM cells and splenic T cells from the same donor mice, V beta 6+ cells were not eliminated at all any periods after BMT. Significantly high number of V beta 6+ SP thymocytes seen 1 week after BMT were shown to be the splenic T cellsinjected with BM cells or their descendants. By contrast, the proportions of the V beta 6+ SP cells in GVHR chimeras 5 weeks after BMT fell within the same range as those of normal donor mice. These V beta 6+ cells were derived from BM precursors. These results reveal that acute GVHR in the thymus results in abrogation of clonal elimination of self reactive T cells in the thymus.
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Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
D000818:Animals; D001854:Bone Marrow Cells; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002454:Cell Differentiation; D002678:Chimera / Q000276:immunology*; D006087:Graft vs Host Reaction; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D051379:Mice; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D000949:Histocompatibility Antigens Class II