Abstract
CD73 (5'-ectonucleotidase) is expressed by two distinct mouse CD4 T cell populations: CD25+ (FoxP3+) T regulatory (Treg) cells that suppress T cell proliferation but do not secrete IL-2, and CD25- uncommitted primed precursor Th (Thpp) cells that secrete IL-2 but do not suppress in standard Treg suppressor assays. CD73 on both Treg and Thpp cells converted extracellular 5'-AMP to adenosine. Adenosine suppressed proliferation and cytokine secretion of Th1 and Th2 effector cells, even when target cells were activated by anti-CD3 and anti-CD28. This represents an additional suppressive mechanism of Treg cells and a previously unrecognized suppressive activity of Thpp cells. Infiltration of either Treg or Thpp cells at inflammatory sites could potentially convert 5'-AMP generated by neutrophils or dying cells into the anti-inflammatory mediator adenosine, thus dampening excessive immune reactions.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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5'-Nucleotidase / biosynthesis
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5'-Nucleotidase / physiology*
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Adenosine / metabolism*
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Adenosine / physiology
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Adenosine Monophosphate / metabolism*
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Animals
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CD4-Positive T-Lymphocytes / enzymology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / pathology
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Cell Proliferation
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Cells, Cultured
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Coculture Techniques
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Cytokines / antagonists & inhibitors
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Cytokines / biosynthesis
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Female
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Growth Inhibitors / biosynthesis
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Growth Inhibitors / physiology*
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Hybridomas
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Inflammation Mediators / metabolism
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Inflammation Mediators / physiology*
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Mice
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Mice, Inbred C57BL
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Stem Cells / enzymology
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Stem Cells / immunology
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Stem Cells / pathology
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T-Lymphocyte Subsets / enzymology
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes, Regulatory / enzymology*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / pathology
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Th1 Cells / enzymology
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Th1 Cells / immunology
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Th1 Cells / pathology
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Th2 Cells / enzymology
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Th2 Cells / immunology
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Th2 Cells / pathology
Substances
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Cytokines
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Growth Inhibitors
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Inflammation Mediators
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Adenosine Monophosphate
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5'-Nucleotidase
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Adenosine