Abstract
Naturally occurring Foxp3+CD4+ regulatory T cells (Tregs) are essential for maintaining immunological self-tolerance and immune homeostasis. Here, we show that a specific deficiency of cytotoxic T lymphocyte antigen 4 (CTLA-4) in Tregs results in spontaneous development of systemic lymphoproliferation, fatal T cell-mediated autoimmune disease, and hyperproduction of immunoglobulin E in mice, and it also produces potent tumor immunity. Treg-specific CTLA-4 deficiency impairs in vivo and in vitro suppressive function of Tregs-in particular, Treg-mediated down-regulation of CD80 and CD86 expression on dendritic cells. Thus, natural Tregs may critically require CTLA-4 to suppress immune responses by affecting the potency of antigen-presenting cells to activate other T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Presenting Cells / immunology
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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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Autoimmune Diseases / immunology
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Autoimmunity*
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B7-1 Antigen / metabolism
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B7-2 Antigen / metabolism
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CD8-Positive T-Lymphocytes / immunology
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CTLA-4 Antigen
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Dendritic Cells / immunology
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Down-Regulation
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Female
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Immune Tolerance*
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Immunoglobulin E / blood
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Immunoglobulin G / blood
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Leukemia / immunology
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Lymphocyte Activation
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Lymphocytes / immunology
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Male
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Mice
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Mice, Inbred BALB C
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T-Lymphocytes, Regulatory / immunology*
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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CTLA-4 Antigen
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Ctla4 protein, mouse
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Immunoglobulin G
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Immunoglobulin E