| RRC ID |
6541
|
| 著者 |
Hirata S, Matsuyoshi H, Fukuma D, Kurisaki A, Uemura Y, Nishimura Y, Senju S.
|
| タイトル |
Involvement of regulatory T cells in the experimental autoimmune encephalomyelitis-preventive effect of dendritic cells expressing myelin oligodendrocyte glycoprotein plus TRAIL.
|
| ジャーナル |
J Immunol
|
| Abstract |
We previously reported the protection from myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) by the adoptive transfer of genetically modified embryonic stem cell-derived dendritic cells (ES-DC) presenting MOG peptide in the context of MHC class II molecules and simultaneously expressing TRAIL (ES-DC-TRAIL/MOG). In the present study, we found the severity of EAE induced by another myelin autoantigen, myelin basic protein, was also decreased after treatment with ES-DC-TRAIL/MOG. This preventive effect diminished, if the function of CD4(+)CD25(+) regulatory T cells (Treg) was abrogated by the injection of anti-CD25 mAb into mice before treatment with ES-DC-TRAIL/MOG. The adoptive transfer of CD4(+)CD25(+) T cells from ES-DC-TRAIL/MOG-treated mice protected the recipient mice from MOG- or myelin basic protein-induced EAE. The number of Foxp3(+) cells increased in the spinal cords of mice treated with ES-DC-TRAIL/MOG. In vitro experiments showed that TRAIL expressed in genetically modified ES-DC and also in LPS-stimulated splenic macrophages had a capacity to augment the proliferation of CD4(+)CD25(+) T cells. These results suggest that the prevention of EAE by treatment with ES-DC-TRAIL/MOG is mediated, at least in part, by MOG-reactive CD4(+)CD25(+) Treg propagated by ES-DC-TRAIL/MOG. For the treatment of organ-specific autoimmune diseases, induction of Treg reactive to the organ-specific autoantigens by the transfer of DC-presenting Ags and simultaneously overexpressing TRAIL therefore appears to be a promising strategy.
|
| 巻・号 |
178(2)
|
| ページ |
918-25
|
| 公開日 |
2007-1-15
|
| DOI |
10.4049/jimmunol.178.2.918
|
| PII |
178/2/918
|
| PMID |
17202353
|
| MeSH |
Adoptive Transfer
Animals
Antibodies, Monoclonal / immunology
Antigen-Presenting Cells / drug effects
Antigen-Presenting Cells / immunology
Cell Movement
Cell Proliferation
Cells, Cultured
Dendritic Cells / cytology
Dendritic Cells / immunology*
Dendritic Cells / metabolism
Embryonic Stem Cells / cytology
Embryonic Stem Cells / metabolism
Encephalomyelitis, Autoimmune, Experimental / drug therapy*
Encephalomyelitis, Autoimmune, Experimental / immunology*
Encephalomyelitis, Autoimmune, Experimental / metabolism
Encephalomyelitis, Autoimmune, Experimental / pathology
Forkhead Transcription Factors / metabolism
Genetic Engineering
Interleukin-2 Receptor alpha Subunit / metabolism
Lipopolysaccharides / pharmacology
Mice
Myelin Basic Protein / pharmacology
Myelin Proteins
Myelin-Associated Glycoprotein / genetics
Myelin-Associated Glycoprotein / metabolism*
Myelin-Associated Glycoprotein / therapeutic use
Myelin-Oligodendrocyte Glycoprotein
Spinal Cord / pathology
T-Lymphocytes, Regulatory / cytology
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / metabolism*
TNF-Related Apoptosis-Inducing Ligand / genetics
TNF-Related Apoptosis-Inducing Ligand / metabolism*
TNF-Related Apoptosis-Inducing Ligand / therapeutic use
|
| IF |
4.886
|
| 引用数 |
35
|
|
WOS 分野
|
IMMUNOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
|
