Abstract
Immunologic tolerance in T lymphocytes is maintained through both thymic and peripheral contributions. One peripheral tolerance mechanism is the induction of T cell anergy, a form of nonresponsiveness resulting from incomplete T cell activation, such as stimulation through the TCR in the absence of costimulation. Recent reports have suggested that engagement of the inhibitory receptor CTLA-4 by its B7 ligand is critical for the initiation of anergy. We tested the importance of CTLA-4 in anergy induction in primary T cells with an in vitro anergy system. Using both CTLA-4/B7-blocking agents and CTLA-4-deficient T cells, we found that T cell anergy can be established in the absence of CTLA-4 expression and/or function. Even in the absence of CTLA-4 signal transduction, T cells activated solely through TCR ligation lose the ability to proliferate as a result of autocrine IL-2 production upon subsequent receptor engagement. Thus, CTLA-4 signaling is not required for the development of T cell anergy.
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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Amino Acid Sequence
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Animals
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Antibodies, Blocking / pharmacology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / genetics
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Antigens, CD / metabolism*
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Antigens, Differentiation / genetics
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Antigens, Differentiation / immunology
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Antigens, Differentiation / metabolism*
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Antigens, Differentiation / pharmacology
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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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CTLA-4 Antigen
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Cell Line
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Clonal Anergy* / genetics
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Clone Cells
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Female
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Immunoconjugates*
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Molecular Sequence Data
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism*
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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Antigens, CD
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Antigens, Differentiation
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B7-1 Antigen
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B7-2 Antigen
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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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Abatacept