title: IFN-γ receptor deficiency prevents diabetes induction by diabetogenic CD4+, but not CD8+, T cells.
abstract: IFN-γ is generally believed to be important in the autoimmune pathogenesis of type 1 diabetes (T1D). However, the development of spontaneous β-cell autoimmunity is unaffected in NOD mice lacking expression of IFN-γ or the IFN-γ receptor (IFNγR), bringing into question the role IFN-γ has in T1D. In the current study, an adoptive transfer model was employed to define the contribution of IFN-γ in CD4(+) versus CD8(+) T cell-mediated β-cell autoimmunity. NOD.scid mice lacking expression of the IFNγR β chain (NOD.scid.IFNγRB(null)) developed diabetes following transfer of β cell-specific CD8(+) T cells alone. In contrast, β cell-specific CD4(+) T cells alone failed to induce diabetes despite significant infiltration of the islets in NOD.scid.IFNγRB(null) recipients. The lack of pathogenicity of CD4(+) T-cell effectors was due to the resistance of IFNγR-deficient β cells to inflammatory cytokine-induced cell death. On the other hand, CD4(+) T cells indirectly promoted β-cell destruction by providing help to CD8(+) T cells in NOD.scid.IFNγRB(null) recipients. These results demonstrate that IFN-γR may play a key role in CD4(+) T cell-mediated β-cell destruction.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Zuoan
authors.initials: Z
authors.lastname: Yi
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Alaina
authors.initials: A
authors.lastname: Garland
authors.forename: Qiuming
authors.initials: Q
authors.lastname: He
authors.forename: Haidong
authors.initials: H
authors.lastname: Wang
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Katz
authors.forename: Roland
authors.initials: R
authors.lastname: Tisch
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D017471:Receptors, Interferon / Q000172:deficiency / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor