Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, NC 27599, USA.
Eur J Immunol. 2012 Aug;42(8):2010-8. doi: 10.1002/eji.201142374.
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.
γ-干扰素（IFN-γ）通常被认为在 1 型糖尿病（T1D）的自身免疫发病机制中起重要作用。然而，在缺乏 IFN-γ 或 IFN-γ 受体（IFNγR）表达的 NOD 小鼠中，自发性β细胞自身免疫的发展不受影响，这使得 IFN-γ 在 T1D 中的作用受到质疑。在本研究中，采用过继转移模型来确定 IFN-γ 在 CD4(+)与 CD8(+)T 细胞介导的β细胞自身免疫中的作用。缺乏 IFNγRβ 链表达的 NOD.scid 小鼠（NOD.scid.IFNγRB(null)）在单独转移β细胞特异性 CD8(+)T 细胞后发生糖尿病。相比之下，β细胞特异性 CD4(+)T 细胞单独转移未能诱导糖尿病，尽管在 NOD.scid.IFNγRB(null)受体内胰岛有明显浸润。CD4(+)T 细胞效应物缺乏致病性是由于 IFNγR 缺陷的β细胞对炎性细胞因子诱导的细胞死亡具有抗性。另一方面，CD4(+)T 细胞通过在 NOD.scid.IFNγRB(null)受体内为 CD8(+)T 细胞提供帮助间接促进β细胞破坏。这些结果表明，IFNγR 可能在 CD4(+)T 细胞介导的β细胞破坏中起关键作用。
