title: T-cell production of an inducible interleukin-10 transgene provides limited protection from autoimmune diabetes.
abstract: In a number of animal models of spontaneous autoimmune diabetes, pathogenesis has been highly correlated with autoreactive T-cell production of the type 1 cytokine interferon-gamma (IFN-gamma), while protection from disease was associated with type 2 cytokines such as interleukin (IL)-4. Curiously, in some models, diabetes is associated with unexpected cytokine patterns; for example, diabetes can develop in NOD mice lacking a functional IFN-gamma gene. In another situation, acceleration of diabetes occurs in transgenic mice with constitutive beta-cell expression of the type 2 cytokine IL-10. IL-10 has generally been associated with immunosuppression, including the modulation of class II expression on antigen-presenting cells and the generation of regulatory CD4 T-cells. Because it is possible that unregulated expression of any cytokine might lead to unphysiological effects in vivo, we tested the notion that an inducible T-cell-specific IL-10 transgene might yet mediate a more physiological protection from autoimmune diabetes. Our results show that indeed, regulated T-cell production of IL-10 does not accelerate diabetes and instead can provide significant protection from disease. These results help rectify the apparent discrepancies between the effect of IL-10 on various models of autoimmune diabetes.
authors.affiliation: Department of Immunology, The Scripps Research Institute, La Jolla, San Diego, California 92037, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Pauza
authors.forename: H
authors.initials: H
authors.lastname: Neal
authors.forename: A
authors.initials: A
authors.lastname: Hagenbaugh
authors.forename: H
authors.initials: H
authors.lastname: Cheroutre
authors.forename: D
authors.initials: D
authors.lastname: Lo
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D013601:T-Lymphocytes / Q000378:metabolism*; D019076:Transgenes
chemical_list: D016753:Interleukin-10