論文 - 詳細
| RRC ID | 6507 |
|---|---|
| 著者 | Hirata S, Senju S, Matsuyoshi H, Fukuma D, Uemura Y, Nishimura Y. |
| タイトル | Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand. |
| ジャーナル | J Immunol |
| Abstract |
Experimental autoimmune encephalomyelitis (EAE) is caused by activation of myelin Ag-reactive CD4+ T cells. In the current study, we tested a strategy to prevent EAE by pretreatment of mice with genetically modified dendritic cells (DC) presenting myelin oligodendrocyte glycoprotein (MOG) peptide in the context of MHC class II molecules and simultaneously expressing TRAIL or Programmed Death-1 ligand (PD-L1). For genetic modification of DC, we used a recently established method to generate DC from mouse embryonic stem cells (ES cells) in vitro (ES-DC). ES cells were sequentially transfected with an expression vector for TRAIL or PD-L1 and an MHC class II-associated invariant chain-based MOG epitope-presenting vector. Subsequently, double-transfectant ES cell clones were induced to differentiate to ES-DC, which expressed the products of introduced genes. Treatment of mice with either of the double-transfectant ES-DC significantly reduced T cell response to MOG, cell infiltration into spinal cord, and the severity of MOG peptide-induced EAE. In contrast, treatment with ES-DC expressing MOG alone, irrelevant Ag (OVA) plus TRAIL, or OVA plus PD-L1, or coinjection with ES-DC expressing MOG plus ES-DC-expressing TRAIL or PD-L1 had no effect in reducing the disease severity. In contrast, immune response to irrelevant exogenous Ag (keyhole limpet hemocyanin) was not impaired by treatment with any of the genetically modified ES-DC. The double-transfectant ES-DC presenting Ag and simultaneously expressing immune-suppressive molecules may well prove to be an effective therapy for autoimmune diseases without inhibition of the immune response to irrelevant Ag. |
| 巻・号 | 174(4) |
| ページ | 1888-97 |
| 公開日 | 2005-2-15 |
| DOI | 10.4049/jimmunol.174.4.1888 |
| PII | 174/4/1888 |
| PMID | 15699115 |
| MeSH | Adoptive Transfer / methods Amino Acid Sequence Animals Apoptosis / genetics Apoptosis / immunology Apoptosis Regulatory Proteins B7-1 Antigen / administration & dosage* B7-1 Antigen / biosynthesis B7-1 Antigen / genetics B7-H1 Antigen CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / pathology Cell Line Crosses, Genetic Dendritic Cells / immunology Dendritic Cells / metabolism Dendritic Cells / transplantation* Down-Regulation / genetics Down-Regulation / immunology Encephalomyelitis, Autoimmune, Experimental / immunology* Encephalomyelitis, Autoimmune, Experimental / pathology Encephalomyelitis, Autoimmune, Experimental / prevention & control* Female Glycoproteins / administration & dosage* Glycoproteins / biosynthesis Glycoproteins / genetics Glycoproteins / immunology Lymphocyte Count Male Membrane Glycoproteins / administration & dosage* Membrane Glycoproteins / biosynthesis Membrane Glycoproteins / genetics Mice Mice, Inbred C57BL Mice, Inbred CBA Molecular Sequence Data Myelin-Oligodendrocyte Glycoprotein Peptide Fragments / administration & dosage* Peptide Fragments / biosynthesis Peptide Fragments / genetics Peptide Fragments / immunology Peptides / administration & dosage* Peptides / genetics Protein Engineering Stem Cell Transplantation / methods* T-Lymphocyte Subsets / immunology T-Lymphocyte Subsets / transplantation TNF-Related Apoptosis-Inducing Ligand Transfection Transgenes / immunology Tumor Necrosis Factor-alpha / administration & dosage* Tumor Necrosis Factor-alpha / biosynthesis Tumor Necrosis Factor-alpha / genetics |
| IF | 4.886 |
| 引用数 | 95 |
| WOS 分野 | IMMUNOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | |