Abstract
It is controversial how cytotoxic T lymphocyte antigen (CTLA)-4, a co-inhibitory molecule, contributes to immunological tolerance and negative control of immune responses. Its role as an inducer of cell-intrinsic negative signals to activated effector T cells is well documented. However, there is accumulating evidence that CTLA-4 is essential for the function of naturally occurring Foxp3(+) regulatory T (Treg) cells, which constitutively express the molecule. CTLA-4 deficiency in Foxp3(+) Treg cells indeed impairs their in vivo and in vitro suppressive function. Further, Treg cells can modulate the function of CD80- and CD86-expressing antigen-presenting cells via CTLA-4. Here we discuss how CTLA-4 expression by one T cell can influence the activation of another in a cell non-autonomous fashion and thus control immune responses.
Copyright © 2011 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antibodies, Neutralizing / pharmacology
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Antigen-Presenting Cells / cytology
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Antigen-Presenting Cells / immunology*
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Antigen-Presenting Cells / metabolism
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Autoimmune Diseases / immunology*
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Autoimmune Diseases / pathology
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Autoimmune Diseases / therapy
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B7-1 Antigen / immunology
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B7-1 Antigen / metabolism
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B7-2 Antigen / immunology
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B7-2 Antigen / metabolism
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CTLA-4 Antigen* / antagonists & inhibitors
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CTLA-4 Antigen* / deficiency
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CTLA-4 Antigen* / genetics
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Cell Communication / immunology
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Forkhead Transcription Factors / immunology
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Homeostasis / immunology
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Immune Tolerance / drug effects
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Immunity*
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Immunotherapy / methods
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Lymphocyte Activation / immunology
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Mice
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Mice, Knockout
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Signal Transduction / immunology*
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
Substances
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Antibodies, Neutralizing
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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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FOXP3 protein, human
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Forkhead Transcription Factors
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Foxp3 protein, mouse