title: Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice.
abstract: Th17 cells are involved in the pathogenesis of many autoimmune diseases, but it is not clear whether they play a pathogenic role in type 1 diabetes. Here we investigated whether mouse Th17 cells with specificity for an islet antigen can induce diabetes upon transfer into NOD/SCID recipient mice. Induction of diabetes in NOD/SCID mice via adoptive transfer of Th1 cells from BDC2.5 transgenic mice was prevented by treatment of the recipient mice with a neutralizing IFN-γ-specific antibody. This result suggested a major role of Th1 cells in the induction of disease in this model of type 1 diabetes. Nevertheless, transfer of highly purified Th17 cells from BDC2.5 transgenic mice caused diabetes in NOD/SCID recipients with similar rates of onset as in transfer of Th1 cells. However, treatment with neutralizing IL-17-specific antibodies did not prevent disease. Instead, the transferred Th17 cells, completely devoid of IFN-γ at the time of transfer, rapidly converted to secrete IFN-γ in the NOD/SCID recipients. Purified Th17 cells also upregulated Tbet and secreted IFN-γ upon exposure to IL-12 in vitro and in vivo in NOD/SCID recipients. These results indicate substantial plasticity of Th17 commitment toward a Th1-like profile.
authors.affiliation: Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Bending
authors.forename: Hugo
authors.initials: H
authors.lastname: De la Peña
authors.forename: Marc
authors.initials: M
authors.lastname: Veldhoen
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Phillips
authors.forename: Catherine
authors.initials: C
authors.lastname: Uyttenhove
authors.forename: Brigitta
authors.initials: B
authors.lastname: Stockinger
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000494:pharmacology; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics; D010179:Pancreas / Q000166:cytology / Q000276:immunology; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053707:Receptors, Interleukin-12 / Q000235:genetics; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D058504:Th17 Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D015854:Up-Regulation / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D007371:Interferon-gamma; D018664:Interleukin-12; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018336:Receptors, Aryl Hydrocarbon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D020825:T-Box Domain Proteins; D029867:Xenopus Proteins; C508440:Il12rb1 protein, mouse; C508443:Il12rb2 protein, mouse; C539901:Rorc protein, mouse; C476769:aryl hydrocarbon receptor, Xenopus; C528688:interleukin-23 receptor, mouse