title: Encephalitogenic T cells that stably express both T-bet and ROR gamma t consistently produce IFNgamma but have a spectrum of IL-17 profiles.
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.
authors.affiliation: Dept. of Pathology, Harvard Medical School, Boston, MA 02115, USA. sara.abromson.leeman@gmail.com
authors.forename: Sara
authors.initials: S
authors.lastname: Abromson-Leeman
authors.forename: Roderick T
authors.initials: RT
authors.lastname: Bronson
authors.forename: Martin E
authors.initials: ME
authors.lastname: Dorf
mesh_terms: 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
chemical_list: 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
references.citation: Curr Opin Immunol. 2006 Jun;18(3):349-56
references.pmid: 16616472
references.citation: J Neuroimmunol. 2007 Feb;183(1-2):96-103
references.pmid: 17240458
references.citation: J Immunol. 1986 Apr 1;136(7):2348-57
references.pmid: 2419430
references.citation: Eur J Immunol. 2009 Mar;39(3):658-61
references.pmid: 19283717
references.citation: J Exp Med. 2008 Jul 7;205(7):1517-22
references.pmid: 18591407
references.citation: J Immunol. 2008 Jun 1;180(11):7414-22
references.pmid: 18490741
references.citation: J Clin Invest. 2009 Mar;119(3):565-72
references.pmid: 19188681
references.citation: Cell. 2000 Mar 17;100(6):655-69
references.pmid: 10761931
references.citation: Curr Opin Immunol. 2007 Jun;19(3):281-6
references.pmid: 17433650
references.citation: Arthritis Rheum. 2007 Sep;56(9):2936-46
references.pmid: 17763419
references.citation: Nature. 2006 May 11;441(7090):235-8
references.pmid: 16648838
references.citation: Immunity. 2006 Feb;24(2):179-89
references.pmid: 16473830
references.citation: Blood. 2006 Sep 1;108(5):1595-601
references.pmid: 16670261
references.citation: Am J Pathol. 2004 Nov;165(5):1519-33
references.pmid: 15509523
references.citation: Nat Immunol. 2005 Nov;6(11):1133-41
references.pmid: 16200068
references.citation: Nat Immunol. 2007 Sep;8(9):950-7
references.pmid: 17676044
references.citation: Immunity. 2009 Jan 16;30(1):92-107
references.pmid: 19119024
references.citation: Eur J Immunol. 2009 Jan;39(1):216-24
references.pmid: 19130584
references.citation: J Exp Med. 2005 Jan 17;201(2):233-40
references.pmid: 15657292
references.citation: J Invest Dermatol. 2008 May;128(5):1207-11
references.pmid: 18200064
references.citation: Nat Med. 2007 Apr;13(4):423-31
references.pmid: 17384649
references.citation: J Immunol. 2008 Nov 15;181(10):7205-13
references.pmid: 18981142
references.citation: J Neuroimmunol. 2007 Dec;192(1-2):3-12
references.pmid: 17976744
references.citation: Immunity. 2008 Apr;28(4):445-53
references.pmid: 18400187
references.citation: J Exp Med. 2007 Aug 6;204(8):1849-61
references.pmid: 17635957
references.citation: Semin Immunol. 2007 Dec;19(6):409-17
references.pmid: 18053739
references.citation: Immunity. 2009 Jan 16;30(1):155-67
references.pmid: 19144320
references.citation: Nature. 2006 May 11;441(7090):231-4
references.pmid: 16648837
references.citation: Arthritis Rheum. 2008 Mar;58(3):875-87
references.pmid: 18311821
references.citation: J Immunol. 2007 Feb 1;178(3):1341-8
references.pmid: 17237380
references.citation: J Exp Med. 2008 Aug 4;205(8):1903-16
references.pmid: 18663128
references.citation: Nat Immunol. 2007 Jun;8(6):639-46
references.pmid: 17486092
references.citation: J Exp Med. 2008 Apr 14;205(4):799-810
references.pmid: 18391061
references.citation: Nature. 2007 Jul 26;448(7152):480-3
references.pmid: 17581589
references.citation: Cell. 2006 Sep 22;126(6):1121-33
references.pmid: 16990136