Abstract
In naive animals, gammadelta T cells are innate sources of IL-17, a potent proinflammatory cytokine mediating bacterial clearance as well as autoimmunity. However, mechanisms underlying the generation of these cells in vivo remain unclear. In this study, we show that TGF-beta1 plays a key role in the generation of IL-17(+) gammadelta T cells and that it mainly occurs in the thymus particularly during the postnatal period. Interestingly, IL-17(+) gammadelta TCR(+) thymocytes were mainly CD44(high)CD25(low) cells, which seem to derive from double-negative 4 gammadelta TCR(+) cells that acquired CD44 and IL-17 expression. Our findings identify a novel developmental pathway during which IL-17-competent gammadelta T cells arise in the thymus by a TGF-beta1-dependent mechanism.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Animals, Newborn
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism*
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Interleukin-17 / biosynthesis*
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Interleukin-17 / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Antigen, T-Cell, gamma-delta / biosynthesis*
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Receptors, Transforming Growth Factor beta / biosynthesis
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Receptors, Transforming Growth Factor beta / genetics
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Thymus Gland / cytology
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Thymus Gland / immunology*
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Thymus Gland / metabolism*
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism
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Transforming Growth Factor beta1 / physiology*
Substances
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Interleukin-17
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Transforming Growth Factor beta
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Tgfb1 protein, mouse
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Transforming Growth Factor beta1