Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells.
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 immunosu...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3471819?pdf=render |
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| author | Yeli Gong Zhigang Wang Zhihui Liang Hongxia Duan Lichen Ouyang Qian Yu Zhe Xu Guanxin Shen Xiufang Weng Xiongwen Wu |
| author_facet | Yeli Gong Zhigang Wang Zhihui Liang Hongxia Duan Lichen Ouyang Qian Yu Zhe Xu Guanxin Shen Xiufang Weng Xiongwen Wu |
| author_sort | Yeli Gong |
| collection | DOAJ |
| description | 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-β (mTGF-β) 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. |
| first_indexed | 2024-12-21T14:21:05Z |
| format | Article |
| id | doaj.art-6044dcde215c48b1a26e225719883bcd |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T14:21:05Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-6044dcde215c48b1a26e225719883bcd2022-12-21T19:00:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01710e4743510.1371/journal.pone.0047435Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells.Yeli GongZhigang WangZhihui LiangHongxia DuanLichen OuyangQian YuZhe XuGuanxin ShenXiufang WengXiongwen WuThe 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-β (mTGF-β) 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.http://europepmc.org/articles/PMC3471819?pdf=render |
| spellingShingle | Yeli Gong Zhigang Wang Zhihui Liang Hongxia Duan Lichen Ouyang Qian Yu Zhe Xu Guanxin Shen Xiufang Weng Xiongwen Wu Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. PLoS ONE |
| title | Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. |
| title_full | Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. |
| title_fullStr | Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. |
| title_full_unstemmed | Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. |
| title_short | Soluble MOG35-55/I-A(b) dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic T cells. |
| title_sort | soluble mog35 55 i a b dimers ameliorate experimental autoimmune encephalomyelitis by reducing encephalitogenic t cells |
| url | http://europepmc.org/articles/PMC3471819?pdf=render |
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