title: A distinct role of CD4+ Th17- and Th17-stimulated CD8+ CTL in the pathogenesis of type 1 diabetes and experimental autoimmune encephalomyelitis.
abstract: Both CD4(+) Th17-cells and CD8(+) cytotoxic T lymphocytes (CTLs) are involved in type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). However, their relationship in pathogenesis of these autoimmune diseases is still elusive. We generated ovalbumin (OVA)- or myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells expressing RORγt and IL-17 by in vitro co-culturing OVA-pulsed and MOG(35-55) peptide-pulsed dendritic cells (DC(OVA) and DC(MOG)) with CD4(+) T cells derived from transgenic OTII and MOG-T cell receptor mice, respectively. We found that these Th17 cells when transferred into C57BL/6 mice stimulated OVA- and MOG-specific CTL responses, respectively. To assess the above question, we adoptively transferred OVA-specific Th17 cells into transgenic rat insulin promoter (RIP)-mOVA mice or RIP-mOVA mice treated with anti-CD8 antibody to deplete Th17-stimulated CD8(+) T cells. We demonstrated that OVA-specific Th17-stimulated CTLs, but not Th17 cells themselves, induced diabetes in RIP-mOVA. We also transferred MOG-specific Th17 cells into C57BL/6 mice and H-2K(b-/-) mice lacking of the ability to generate Th17-stimulated CTLs. We further found that MOG-specific Th17 cells, but not Th17-activated CTLs induced EAE in C57BL/6 mice. Taken together, our data indicate a distinct role of Th17 cells and Th17-stimulated CTLs in the pathogenesis of TID and EAE, which may have great impact on the overall understanding of Th17 cells in the pathogenesis of autoimmune diseases.
authors.affiliation: Research Unit, Saskatchewan Cancer Agency, Department of Oncology, Saskatoon Cancer Center, 20 Campus Drive, Saskatoon, Saskatchewan, S7N 4H4, Canada.
authors.forename: Manjunatha
authors.initials: M
authors.lastname: Ankathatti Munegowda
authors.forename: Yulin
authors.initials: Y
authors.lastname: Deng
authors.forename: Rajni
authors.initials: R
authors.lastname: Chibbar
authors.forename: Qingyong
authors.initials: Q
authors.lastname: Xu
authors.forename: Andrew
authors.initials: A
authors.lastname: Freywald
authors.forename: Sean J
authors.initials: SJ
authors.lastname: Mulligan
authors.forename: Sylvia
authors.initials: S
authors.lastname: van Drunen Littel-van den Hurk
authors.forename: Deming
authors.initials: D
authors.lastname: Sun
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.forename: Jim
authors.initials: J
authors.lastname: Xiang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D063308:Myelin-Oligodendrocyte Glycoprotein; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation
chemical_list: D015704:CD4 Antigens; D016827:CD8 Antigens; D006023:Glycoproteins; D020381:Interleukin-17; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C517781:myelin oligodendrocyte glycoprotein (34-56); D010047:Ovalbumin