Abstract
CD4+CD25+ regulatory T (T(R)) cells suppress effector T cells by partly unknown mechanisms. In this study, we describe a population of human suppressive CD4+CD25+ adaptive T(R) (T(R)(adapt)) cells induced in vitro that express cyclooxygenase 2 (COX-2) and the transcription factor FOXP3. T(R)(adapt) cells produce PGE(2) and suppress effector T cell responses in a manner that is reversed by COX inhibitors and PGE(2) receptor-specific antagonists. In resting CD4+CD25- T cells, treatment with PGE(2) induced FOXP3 expression. Thus, autocrine and paracrine effects of PGE(2) produced by COX-2-positive T(R)(adapt) cells may be responsible for both the FOXP3+ phenotype and the mechanism used by these cells to suppress effector T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cell Communication / immunology
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Cells, Cultured
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Cyclic AMP / biosynthesis
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Cyclooxygenase 2 / biosynthesis*
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Cyclooxygenase 2 Inhibitors / pharmacology
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Dinoprostone / antagonists & inhibitors
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Dinoprostone / biosynthesis
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Dinoprostone / metabolism
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Dinoprostone / physiology*
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Enterotoxins / pharmacology
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Forkhead Transcription Factors / biosynthesis*
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Forkhead Transcription Factors / physiology
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Humans
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Immunity, Innate
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Immunosuppressive Agents / antagonists & inhibitors
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Immunosuppressive Agents / pharmacology
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Lymphocyte Activation / immunology
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Prostaglandin Antagonists / physiology
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Receptors, Interleukin-2 / biosynthesis*
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Receptors, Prostaglandin E / antagonists & inhibitors
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T-Lymphocyte Subsets / enzymology*
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / microbiology
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T-Lymphocytes, Regulatory / enzymology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / microbiology
Substances
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Cyclooxygenase 2 Inhibitors
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Enterotoxins
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FOXP3 protein, human
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Forkhead Transcription Factors
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Immunosuppressive Agents
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Prostaglandin Antagonists
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Receptors, Interleukin-2
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Receptors, Prostaglandin E
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enterotoxin B, staphylococcal
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Cyclic AMP
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Cyclooxygenase 2
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Dinoprostone