title: Regulation of autoimmune diabetes by non-islet-specific T cells - a role for the glucocorticoid-induced TNF receptor.
abstract: Diabetogenic BDC2.5 CD4 T cells induce diabetes when injected into NOD.scid mice. However, when co-transferred with the OVA-specific DO11.10 CD4 T cells, BDC2.5 T cells failed to cause diabetes. This inhibition depended upon the stimulation of DO11.10 T cells only with soluble OVA, which skewed their differentiation to a Th2-type pattern of cytokine secretion in vivo. However, in vivo neutralization of IL-4, IL-10 or TGF-beta using monoclonal antibodies did not prevent the inhibition whereas treatment with an antibody against the glucocorticoid-induced TNF receptor abrogated the protection from disease. In the protected mice, the diabetogenic T cells could be isolated from their spleens and shown to transfer diabetes when injected into new NOD.scid recipients. Thus, the inhibition took place without the physical or functional elimination of the diabetogenic T cells.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Anish
authors.initials: A
authors.lastname: Suri
authors.forename: Jun
authors.initials: J
authors.lastname: Shimizu
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Katz
authors.forename: Shimon
authors.initials: S
authors.lastname: Sakaguchi
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
authors.forename: Osami
authors.initials: O
authors.lastname: Kanagawa
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor