| First Author | Gong Y | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 10 | Pages | e47435 |
| PubMed ID | 23077616 | Mgi Jnum | J:192210 |
| Mgi Id | MGI:5464174 | Doi | 10.1371/journal.pone.0047435 |
| Citation | Gong Y, et al. (2012) Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. PLoS One 7(10):e47435 |
| abstractText | The MOG35-55 peptide-induced experimental autoimmune encephalomyelitis (EAE) model in C57BL/6 mice is a useful animal model to explore therapeutic approaches to T cell-mediated autoimmune diseases because the dominant T-cell epitope(s) have been defined. It is rational that antigen-specific immunosuppression can be induced by using MHC-peptide complexes as specific TCR ligand(s) that interact with autoreactive T cells in the absence of co-stimulation. In this study, a soluble divalent MOG35-55/I-A(b) fusion protein (MOG35-55/I-A(b) dimer) was constructed to specifically target the autoreactive CD4+ T cells in the EAE mouse. Intraperitoneal administration of the MOG35-55/I-A(b) dimer significantly delayed and ameliorated EAE symptoms by reducing EAE-related inflammation in the mouse CNS and reducing encephalitogenic Th1 and Th17 cells in the peripheral lymphoid organs. We observed that dimer intervention at a concentration of 1.2 nM suppressed MOG35-55 peptide-specific 2D2 transgenic T cells (2D2 T cells) proliferation by over 90% after in vitro activation with MOG35-55 peptide. The mechanisms involved in this antigen-specific dimer-mediated suppression were found to be downregulated TCR-CD3 expression as well as upregulated expression of membrane-bound TGF-beta (mTGF-beta) and IL-10 suppressive cytokines by the autoreactive CD4+ T cells. Collectively, our data demonstrates that soluble divalent MHC class II molecules can abrogate pathogenic T cells in EAE. Furthermore, our data suggests that this strategy may provide an efficient and clinically useful option to treat autoimmune diseases. |
