IFN-γ receptor deficiency prevents diabetes induction by diabetogenic CD4+T cells but not CD8+T cells
Year: 2012
Type: article
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.IFNγRBnull) 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.IFNγRBnull 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.IFNγRBnull recipients. These results demonstrate that IFN-γR may play a key role in CD4+ T cell-mediated β cell destruction.
Source: European Journal of Immunology
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4254575485