title: Mouse pancreatic beta cells express MHC class II and stimulate CD4(+) T cells to proliferate.
abstract: Type 1 diabetes results from destruction of pancreatic beta cells by autoreactive T cells. Both CD4(+) and CD8(+) T cells have been shown to mediate beta-cell killing. While CD8(+) T cells can directly recognize MHC class I on beta cells, the interaction between CD4(+) T cells and beta cells remains unclear. Genetic association studies have strongly implicated HLA-DQ alleles in human type 1 diabetes. Here we studied MHC class II expression on beta cells in nonobese diabetic mice that were induced to develop diabetes by diabetogenic CD4(+) T cells with T-cell receptors that recognize beta-cell antigens. Acute infiltration of CD4(+) T cells in islets occurred with rapid onset of diabetes. Beta cells from islets with immune infiltration expressed MHC class II mRNA and protein. Exposure of beta cells to IFN-γ increased MHC class II gene expression, and blocking IFN-γ signaling in beta cells inhibited MHC class II upregulation. IFN-γ also increased HLA-DR expression in human islets. MHC class II(+) beta cells stimulated the proliferation of beta-cell-specific CD4(+) T cells. Our study indicates that MHC class II molecules may play an important role in beta-cell interaction with CD4(+) T cells in the development of type 1 diabetes.
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Scott
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Hong Sheng
authors.initials: HS
authors.lastname: Quah
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.
authors.forename: Balasubramanian
authors.initials: B
authors.lastname: Krishnamurthy
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.
authors.forename: Francene
authors.initials: F
authors.lastname: Bond
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Loudovaris
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Stuart I
authors.initials: SI
authors.lastname: Mannering
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Thomas W H
authors.initials: TW
authors.lastname: Kay
authors.affiliation: St. Vincent's Institute, Immunology and Diabetes Laboratory, Fitzroy, Victoria, Australia.|Department of Medicine, St. Vincent's Hospital, The University of Melbourne, Fitzroy, Victoria, Australia.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Thomas
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006683:HLA-DQ Antigens / Q000235:genetics / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D016688:Mice, Inbred NOD; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D046509:Tissue Culture Techniques
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma
keywords: Autoimmune diabetes · CD4+ T cells · MHC class II · Pancreatic beta cell