Abstract
CD4(+) T cells that undergo multiple rounds of cell division during primary Ag challenge in vivo produce IL-2 on secondary Ag rechallenge, whereas cells that fail to progress through the cell cycle are anergic to restimulation. Anti-CTLA-4 mAb treatment during primary Ag exposure increases cell cycle progression and enhances recall Ag responsiveness; however, simultaneous treatment with rapamycin, an inhibitor of the mammalian target of rapamycin and potent antiproliferative agent, prevents both effects. The data suggest that cell cycle progression plays a primary role in the regulation of recall Ag responsiveness in CD4(+) T cells in vivo. CTLA-4 molecules promote clonal anergy development only indirectly by limiting cell cycle progression during the primary response.
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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Animals
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Antibodies, Monoclonal / pharmacology
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Antigens / immunology
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Antigens, CD
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Antigens, Differentiation / immunology
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Antigens, Differentiation / physiology*
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CTLA-4 Antigen
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Cell Cycle / drug effects
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Cells, Cultured
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Clonal Anergy* / drug effects
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Genes, T-Cell Receptor
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Immunoconjugates*
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Immunologic Memory
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Interleukin-2 / biosynthesis
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Kinetics
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Lymphocyte Activation
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Mice
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Mice, Transgenic
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Protein Kinases / physiology*
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Signal Transduction
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Sirolimus / pharmacology
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TOR Serine-Threonine Kinases
Substances
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Antibodies, Monoclonal
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Antigens
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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, mouse
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Immunoconjugates
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Interleukin-2
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Abatacept
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Protein Kinases
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mTOR protein, mouse
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TOR Serine-Threonine Kinases
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Sirolimus