Encephalitogenic T cells that stably express both T-bet and ROR gamma t consistently produce IFNgamma but have a spectrum of IL-17 profiles.
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.
Abromson-Leeman
Sara
S
Dept. of Pathology, Harvard Medical School, Boston, MA 02115, USA. sara.abromson.leeman@gmail.com
Bronson
Roderick T
RT
Dorf
Martin E
ME
D000818:Animals; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000235:genetics; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis* / Q000235:genetics; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis* / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D000098815:T-bet Transcription Factor
D020381:Interleukin-17; D004676:Myelin Basic Protein; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; C539901:Rorc protein, mouse; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma
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