| First Author | Yi Z | Year | 2012 |
| Journal | Eur J Immunol | Volume | 42 |
| Issue | 8 | Pages | 2010-8 |
| PubMed ID | 22865049 | Mgi Jnum | J:187880 |
| Mgi Id | MGI:5438684 | Doi | 10.1002/eji.201142374 |
| Citation | Yi Z, et al. (2012) IFN-gamma receptor deficiency prevents diabetes induction by diabetogenic CD4+, but not CD8+, T cells. Eur J Immunol 42(8):2010-8 |
| abstractText | IFN-gamma is generally believed to be important in the autoimmune pathogenesis of type 1 diabetes (T1D). However, the development of spontaneous beta-cell autoimmunity is unaffected in NOD mice lacking expression of IFN-gamma or the IFN-gamma receptor (IFNgammaR), bringing into question the role IFN-gamma has in T1D. In the current study, an adoptive transfer model was employed to define the contribution of IFN-gamma in CD4(+) versus CD8(+) T cell-mediated beta-cell autoimmunity. NOD.scid mice lacking expression of the IFNgammaR beta chain (NOD.scid.IFNgammaRB(null)) developed diabetes following transfer of beta cell-specific CD8(+) T cells alone. In contrast, beta cell-specific CD4(+) T cells alone failed to induce diabetes despite significant infiltration of the islets in NOD.scid.IFNgammaRB(null) recipients. The lack of pathogenicity of CD4(+) T-cell effectors was due to the resistance of IFNgammaR-deficient beta cells to inflammatory cytokine-induced cell death. On the other hand, CD4(+) T cells indirectly promoted beta-cell destruction by providing help to CD8(+) T cells in NOD.scid.IFNgammaRB(null) recipients. These results demonstrate that IFN-gammaR may play a key role in CD4(+) T cell-mediated beta-cell destruction. |
