Abstract
Antigen-specific T cell activation depends on T cell receptor-ligand interaction and costimulatory signals generated when accessory molecules bind to their ligands, such as CD28 to the B7 (also called BB1) molecule. A soluble fusion protein of human CTLA-4 (a protein homologous to CD28) and the immunoglobulin (lg) G1 Fc region (CTLA4lg) binds to human and murine B7 with high avidity and blocks T cell activation in vitro. CTLA4lg therapy blocked human pancreatic islet rejection in mice by directly affecting T cell recognition of B7+ antigen-presenting cells. In addition, CTLA4lg induced long-term, donor-specific tolerance, which may have applications to human organ transplantation.
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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Abatacept
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Animals
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Antibodies, Monoclonal / therapeutic use
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Antigens, CD
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Antigens, Differentiation / immunology
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Antigens, Differentiation / therapeutic use*
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CTLA-4 Antigen
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Diabetes Mellitus, Experimental / surgery*
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Graft Survival / immunology*
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Graft Survival / physiology
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Humans
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Immunoconjugates*
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Immunosuppressive Agents / therapeutic use*
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Islets of Langerhans Transplantation / immunology*
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Islets of Langerhans Transplantation / physiology
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Mice
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Mice, Inbred Strains
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Phosphates / analysis
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Phosphates / metabolism*
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Receptors, Cell Surface / immunology
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Recombinant Fusion Proteins / therapeutic use*
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Time Factors
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Transplantation, Heterologous / immunology*
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Transplantation, Heterologous / physiology
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Uranium / analysis
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Uranium / metabolism*
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Uranium Compounds*
Substances
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CTLA-4 Antigen
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CTLA4 protein, human
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Ctla4 protein, mouse
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Immunoconjugates
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Immunoglobulin Fc Fragments
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Immunoglobulin G
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Immunosuppressive Agents
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Phosphates
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Uranium Compounds
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hydrogen uranyl phosphate
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Uranium
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Abatacept