RRC ID 6541
Author Hirata S, Matsuyoshi H, Fukuma D, Kurisaki A, Uemura Y, Nishimura Y, Senju S.
Title Involvement of regulatory T cells in the experimental autoimmune encephalomyelitis-preventive effect of dendritic cells expressing myelin oligodendrocyte glycoprotein plus TRAIL.
Journal 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.
Volume 178(2)
Pages 918-25
Published 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
Times Cited 35
Human and Animal Cells