Abstract
CD28 and CTLA-4 are related glycoproteins found on T cells. Ligation of CD28 following antigen receptor engagement provides a costimulatory signal required for T cell activation. Anti-CTLA-4 antibodies were generated to examine the role of the CTLA-4 receptor on murine T cells. Expression of CTLA-4 as a homodimer is up-regulated 2-3 days following T cell activation. Anti-CTLA-4 antibodies and Fab fragments augmented T cell proliferation in an allogeneic MLR. However, when optimal costimulation and Fc cross-linking were present, anti-CTLA-4 Mabs inhibited T cell proliferation. Together, these results suggest that the MAb may obstruct the interaction of CTLA-4 with its natural ligand and block a negative signal, or directly signal T cells to down-regulate immune function.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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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 / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD
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Antigens, Differentiation / chemistry
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Antigens, Differentiation / immunology
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Antigens, Differentiation / physiology*
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Base Sequence
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CD28 Antigens / pharmacology
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CD3 Complex / immunology
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CTLA-4 Antigen
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Cell Division / immunology
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Humans
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Immunoconjugates*
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Immunoglobulin Fab Fragments
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Immunoglobulin Fragments / immunology
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Immunoglobulin Fragments / pharmacology
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Lymphocyte Activation
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Lymphocyte Culture Test, Mixed
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Male
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Membrane Proteins / chemistry
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Molecular Sequence Data
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Receptors, Antigen, T-Cell / physiology
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T-Lymphocytes / cytology
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T-Lymphocytes / immunology*
Substances
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Antibodies
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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CD28 Antigens
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CD3 Complex
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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 Fab Fragments
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Immunoglobulin Fragments
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Membrane Proteins
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Receptors, Antigen, T-Cell
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Abatacept