Abstract
Th1/Th17 cells, secreting both IFNgamma and IL-17, are often associated with inflammatory pathology. We cloned and studied the cytokine phenotypes of MBP-specific, TCR-identical encephalitogenic CD4+ cells in relationship to Th1- and Th17-associated transcription factors T-bet and RORgammat. IFNgamma-producing cells could be sub-divided into those that are T-bet(+)/RORgammat(-) and those that are T-bet(+)/RORgammat(+). The latter comprises a spectrum of phenotypes, as defined by IL-17 production, and can be induced to up-regulate IL-23R with IL-12 or IL-23. The former, bona fide Th1 cells, lack IL-23R expression under all conditions. In vivo, T-bet(+)/RORgammat(-) and T-bet(+)/RORgammat(+) clones induce EAE equally well.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Clone Cells
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Encephalomyelitis, Autoimmune, Experimental / pathology
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Gene Expression Profiling*
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Immunophenotyping
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Interferon-gamma / biosynthesis*
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Interferon-gamma / genetics
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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 BALB C
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Mice, Transgenic
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Myelin Basic Protein / immunology
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid / biosynthesis*
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Receptors, Retinoic Acid / genetics
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Receptors, Thyroid Hormone / biosynthesis*
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Receptors, Thyroid Hormone / genetics
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T-Box Domain Proteins / biosynthesis*
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T-Box Domain Proteins / genetics
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T-Lymphocytes, Helper-Inducer / immunology*
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Interleukin-17
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Myelin Basic Protein
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Nuclear Receptor Subfamily 1, Group F, Member 3
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Receptors, Retinoic Acid
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Receptors, Thyroid Hormone
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Rorc protein, mouse
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Interferon-gamma