title: Genetic absence of gamma-interferon delays but does not prevent diabetes in NOD mice.
abstract: Cytokines, particularly interferons, may participate in the development of type I diabetes. This involvement could be from direct cytotoxic actions of the interferons on the pancreatic beta-cells or from an indirect influence on the number, activity, or type of inflammatory cells that invade the islets in type I diabetes. To examine directly the role of interferon (IFN)-gamma in a mouse model of type I diabetes, we have introduced an inactivating mutation in the IFN-gamma gene (ifg) into NOD mice. The genetic absence of IFN-gamma does not prevent either insulitis or diabetes in the NOD mice, but it does increase the time to onset. Although it might have been predicted that the absence of IFN-gamma in these mice would lead to an increase in expression of Th2 T-helper cell-related cytokines, we found instead a profound decrease in the expression of two of the characteristic Th2 cytokines, interleukin (IL)-4 and IL-10. We also demonstrate that the splenocytes taken from IFN-gamma-deficient diabetic mice are fully capable of transferring diabetes to naive recipients.
authors.affiliation: Department of Molecular Biology, Genentech, South San Francisco, California, USA.
authors.forename: B
authors.initials: B
authors.lastname: Hultgren
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: N
authors.initials: N
authors.lastname: Dybdal
authors.forename: T A
authors.initials: TA
authors.lastname: Stewart
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D005838:Genotype; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics*; D007515:Islets of Langerhans / Q000254:growth & development / Q000276:immunology* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D016133:Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D007371:Interferon-gamma