title: TGF-beta1 alters APC preference, polarizing islet antigen responses toward a Th2 phenotype.
abstract: TGF-beta1, expressed in the pancreatic islets, protects the nonobese diabetic (NOD) mouse from insulin-dependent diabetes mellitus (IDDM). The islet antigen-specific T cell response of ins-TGF-beta1 mice relied on different antigen-presenting cells (APC) from those used by NOD T cells. T cells from NOD mice utilized B cells to present islet antigen, whereas T cells from ins-TGF-beta1 mice utilized macrophages. In addition, the islet antigen-specific T cell repertoire of ins-TGF-beta1 mice was distinct and deviated toward an IL-4-producing Th2 phenotype. When ins-TGF-beta1 mice were treated with anti-iL-4 antibody, islet antigen-specific IFNGamma-producing Th1 cells were unleashed, and the incidence of diabetes increased to the level of NOD mice. This suggests active suppression of a diabetogenic T cell response. This study describes a novel mechanism in which expression of TGF-beta1 in the context of self-antigen shifts APC preference, deviating T cell responses to a Th2 phenotype, preventing IDDM.
authors.affiliation: Department of Immunology, Scripps Research Institute, La Jolla, California 92037, USA.
authors.forename: C
authors.initials: C
authors.lastname: King
authors.forename: J
authors.initials: J
authors.lastname: Davies
authors.forename: R
authors.initials: R
authors.lastname: Mueller
authors.forename: M S
authors.initials: MS
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Krahl
authors.forename: B
authors.initials: B
authors.lastname: Yeung
authors.forename: E
authors.initials: E
authors.lastname: O'Connor
authors.forename: N
authors.initials: N
authors.lastname: Sarvetnick
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects*; D001324:Autoantigens / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology; D005968:Glutamate Decarboxylase / Q000276:immunology; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D001324:Autoantigens; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D005968:Glutamate Decarboxylase