Abstract
The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.
Publication types
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Research Support, Non-U.S. Gov't
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Comment
MeSH terms
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Abatacept
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Animals
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Antigens, CD / analysis
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Antigens, Differentiation / genetics
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Antigens, Differentiation / physiology*
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Apoptosis
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B-Lymphocytes / immunology
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CTLA-4 Antigen
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Cells, Cultured
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Concanavalin A / pharmacology
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Female
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Gamma Rays
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Gene Targeting
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Homeostasis
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Immunoconjugates*
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Immunoglobulins / blood
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Immunophenotyping
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Lymph Nodes / immunology
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Lymph Nodes / pathology
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Lymphocyte Activation*
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Lymphoproliferative Disorders / immunology*
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Lymphoproliferative Disorders / pathology
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Male
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Mice
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Mice, Inbred C57BL
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Spleen / immunology
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Spleen / pathology
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T-Lymphocytes / immunology*
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fas Receptor / metabolism
Substances
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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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Immunoglobulins
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fas Receptor
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Concanavalin A
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Abatacept