| First Author | Sabatino JJ Jr | Year | 2008 |
| Journal | J Immunol | Volume | 180 |
| Issue | 7 | Pages | 4451-7 |
| PubMed ID | 18354166 | Mgi Jnum | J:132970 |
| Mgi Id | MGI:3777479 | Doi | 10.4049/jimmunol.180.7.4451 |
| Citation | Sabatino JJ Jr, et al. (2008) Loss of IFN-{gamma} Enables the Expansion of Autoreactive CD4+ T Cells to Induce Experimental Autoimmune Encephalomyelitis by a Nonencephalitogenic Myelin Variant Antigen. J Immunol 180(7):4451-7 |
| abstractText | MHC variant peptides are analogues of immunogenic peptides involving alterations of the MHC-binding residues, thereby altering the affinity of the peptide for the MHC molecule. Recently, our laboratory demonstrated that immunization of WT B6 mice with 45D, a low-affinity MHC variant peptide of MOG(35-55), results in significantly attenuated experimental autoimmune encephalomyelitis (EAE), yet IFN-gamma production is comparable to myelin oligodendrocyte glycoprotein (MOG)(35-55)-immunized mice. In light of these findings, we asked whether IFN-gamma was required for the reduced encephalitogenicity of the weak ligand 45D in EAE. In this study, we report that immunization of mice deficient in IFN-gamma or its receptor with 45D exhibit significant EAE signs compared with 45D-immunized wild-type B6 mice. Moreover, 45D-immunized IFN-gamma(-/-) and IFN-gammaR(-/-) mice demonstrate MOG tetramer-positive CD4(+) T cells within the CNS and display substantial numbers of MOG-specific CD4(+) T cells in the periphery. In contrast, wild-type mice immunized with 45D exhibit reduced numbers of MOG-specific CD4(+) T cells in the periphery and lack MOG tetramer- positive CD4(+) T cells in the CNS. Importantly, the increased encephalitogenicity of 45D in mice lacking IFN-gamma or IFN-gammaR was not due to deviation toward an enhanced IL-17-secreting phenotype. These findings demonstrate that IFN-gamma significantly attenuates the encephalitogenicity of 45D and are the first to highlight the importance of IFN-gamma signaling in setting the threshold level of responsiveness of autoreactive CD4(+) T cells to weak ligands. |
