Abstract
IL-17-producing CD4(+) T cells (Th17) have been classified as a new T helper cell subset. Using an IL-17 fate mapping mouse strain, which genetically fixes the memory of IL-17 expression, we demonstrate that IL-17A/F-expressing T helper cells generated either in vitro or in vivo are not a stable T-cell subset. Upon adoptive transfer of IL-17F-reporter-positive Th17 cells to RAG-deficient or WT animals, encephalitogenic Th17 cells partially lose IL-17 expression and upregulate IFN-γ. Additionally, we show that Th1 cells can convert in vivo to IL-17A/IFN-γ-coexpressing cells in the mesenteric lymph nodes (mLN). Our data classify IL-17A and IL-17F as cytokines produced transiently in response to the local microenvironment, thus showing that IL-17 expression does not define an end-stage T helper cell subset.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Cell Differentiation / immunology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Gene Expression Regulation / genetics
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Gene Expression Regulation / immunology*
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Genes, RAG-1 / genetics
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Genes, Reporter / genetics
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Integrases / genetics
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Interferon-gamma / metabolism
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Receptors, Antigen, T-Cell / genetics
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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T-Lymphocyte Subsets / pathology
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Th1 Cells / immunology
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Th1 Cells / metabolism*
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Th1 Cells / pathology
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Th17 Cells / immunology
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Th17 Cells / metabolism*
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Th17 Cells / pathology
Substances
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Receptors, Antigen, T-Cell
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Interferon-gamma
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Cre recombinase
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Integrases