title: CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes.
abstract: CD28 ligation delivers a costimulatory signal important in T cell activation. This study demonstrates that the disruption of the CD28/B7 pathway early in the nonobese diabetic mouse strain, using CD28-/- and CTLA41g transgenic mice, promoted the development and progression of spontaneous autoimmune diabetes. Functional analyses of T cells isolated from CD28-deficient mice demonstrated that the GAD-specific T cells produced enhanced Th1-type cytokines (IL-2 and IFN gamma) and diminished Th2-type cytokine, IL-4. Moreover, there was a significant decrease in serum levels of anti-GAD antibodies of the IgG1 isotype consistent with a profound suppression of Th2-type responses in these animals. Thus, the early differentiation of naive diabetogenic T cells into the Th2 subset is dependent upon CD28 signaling and extends our understanding of the importance of Th1/Th2 balance in the regulation of this spontaneous autoimmune disease.
authors.affiliation: Ben May Institute for Cancer Research, Department of Pathology,  University of Chicago, Illinois 60637, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Lenschow
authors.forename: K C
authors.initials: KC
authors.lastname: Herold
authors.forename: L
authors.initials: L
authors.lastname: Rhee
authors.forename: B
authors.initials: B
authors.lastname: Patel
authors.forename: A
authors.initials: A
authors.lastname: Koons
authors.forename: H Y
authors.initials: HY
authors.lastname: Qin
authors.forename: E
authors.initials: E
authors.lastname: Fuchs
authors.forename: B
authors.initials: B
authors.lastname: Singh
authors.forename: C B
authors.initials: CB
authors.lastname: Thompson
authors.forename: J A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology; D001324:Autoantigens / Q000276:immunology; D018122:B7-1 Antigen / Q000502:physiology*; D001483:Base Sequence; D018106:CD28 Antigens / Q000502:physiology*; D060908:CTLA-4 Antigen; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005968:Glutamate Decarboxylase / Q000276:immunology; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000145:classification; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000276:immunology; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D001324:Autoantigens; D018122:B7-1 Antigen; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007074:Immunoglobulin G; D000069594:Abatacept; D010047:Ovalbumin; D005968:Glutamate Decarboxylase