Abstract
Costimulatory molecules B7-1 and B7-2 (hereby collectively called B7) interact with CD28 and CTLA4 on T cells and promote antitumor immunity. The function of B7-CTLA4 interaction in antitumor CTL response remains controversial. Here we used CD28(-/-) and CD28(+/-) or CD28(+/+) transgenic mice that express the T-cell receptor specific for an unmutated tumor antigen, P1A, and for tumor cells expressing a CTLA4-specific B7 mutant to evaluate the function of CD28-B7 and CTLA4-B7 interactions in induction and effector phases of antitumor immunity. We report that B7-CD28 and B7-CTLA4 interactions promote tumor rejection. However, this is achieved by distinct mechanisms. B7-CD28 interaction enhances T-cell clonal expansion, though a role for this interaction in the effector phase cannot be ruled out. In contrast, B7-CTLA4 interaction enhances the CTL-mediated destruction of tumors, but not T-cell clonal expansion.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abatacept
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Adoptive Transfer
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Animals
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Antigens, CD / genetics
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Antigens, CD / immunology
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Antigens, CD / metabolism
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Antigens, Differentiation / immunology
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Antigens, Differentiation / metabolism*
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Antigens, Neoplasm / immunology*
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology
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B7-1 Antigen / metabolism*
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B7-2 Antigen
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CD28 Antigens / genetics
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CD28 Antigens / metabolism
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CTLA-4 Antigen
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Cytotoxicity, Immunologic / drug effects
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Immunity
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Immunoconjugates*
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Lymphocyte Activation / drug effects
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Transgenic
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Mutation
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Neoplasms, Experimental / therapy
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Protein Binding / immunology
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Receptors, Antigen, T-Cell / immunology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / transplantation
Substances
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Antigens, CD
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Antigens, Differentiation
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Antigens, Neoplasm
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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CTLA-4 Antigen
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Cd86 protein, mouse
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Ctla4 protein, mouse
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Immunoconjugates
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Membrane Glycoproteins
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Receptors, Antigen, T-Cell
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tumor rejection antigen P815A, mouse
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Abatacept