Abstract
Induction of immunological tolerance is highly desirable for the treatment and prevention of autoimmunity, allergy, and organ transplant rejection. Adoptive transfer of MHC class I disparate mature T cells at the time of reconstitution of mice with syngeneic bone marrow resulted in specific tolerance to allogeneic skin grafts that were matched to the T cell donor strain. Mature allogeneic T cells survived long-term in reconstituted hosts and were able to re-enter the thymus. Analysis of T cell development using transgenic mice expressing an alloantigen-reactive TCR revealed that expression of allogeneic MHC class I on adoptively transferred mature T cells mediated negative selection of developing alloreactive T cells in the thymus. Thus, mature allogeneic T cells are able to mediate central deletion of alloreactive cells and induce transplantation tolerance without the requirement for any other alloantigen-expressing cell type.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / transplantation
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Bone Marrow Transplantation / immunology
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CD8-Positive T-Lymphocytes / cytology
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CD8-Positive T-Lymphocytes / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Survival / genetics
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Cell Survival / immunology
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Female
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Graft Rejection / genetics
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Graft Rejection / immunology
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H-2 Antigens / biosynthesis
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H-2 Antigens / genetics
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Histocompatibility Testing
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Mice
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Mice, Inbred CBA
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Mice, Transgenic
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Radiation Chimera
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation*
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Thymus Gland / cytology
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Thymus Gland / immunology
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Transplantation Conditioning / methods
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Transplantation Tolerance* / genetics
Substances
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H-2 Antigens
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H-2Kb protein, mouse