Abstract
CD28/B7 blockade leads to exacerbated autoimmune disease in the nonobese diabetic mouse strain as a result of a marked reduction in the number of CD4(+)CD25(+) regulatory T cells (Tregs). Herein, we demonstrate that CD28 controls both thymic development and peripheral homeostasis of Tregs. CD28 maintains a stable pool of peripheral Tregs by both supporting their survival and promoting their self-renewal. CD28 engagement promotes survival by regulating IL-2 production by conventional T cells and CD25 expression on Tregs.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Antigens, CD / pharmacology
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Antigens, CD / physiology
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B7-1 Antigen / pharmacology
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B7-1 Antigen / physiology
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B7-2 Antigen
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CD28 Antigens / metabolism
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CD28 Antigens / physiology*
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CD4-Positive T-Lymphocytes / cytology*
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation / immunology
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Cell Division / immunology
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Cell Survival / immunology
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Homeostasis / immunology*
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Interleukin-2 / physiology
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Lymph Nodes / cytology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Membrane Glycoproteins / pharmacology
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Membrane Glycoproteins / physiology
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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 NOD
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Mice, Knockout
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Mice, Transgenic
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Receptors, Interleukin-2 / biosynthesis*
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Spleen / cytology
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Spleen / immunology
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Spleen / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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Thymus Gland / cytology
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Thymus Gland / immunology
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Thymus Gland / metabolism
Substances
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Antigens, CD
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B7-1 Antigen
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B7-2 Antigen
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CD28 Antigens
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Cd86 protein, mouse
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Interleukin-2
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Membrane Glycoproteins
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Receptors, Interleukin-2