Role of MOG-stimulated Th1 type "light up" (GFP+) CD4+ T cells for the development of experimental autoimmune encephalomyelitis (EAE).
Experimental autoimmune encephalomyelitis (EAE) is an animal model for multiple sclerosis in humans. EAE can be passively transferred into naive syngeneic animals by administration of MOG-specific T cell clones. Lymphocytes isolated from green fluorescent protein (GFP)-transgenic (Tg) mice can light up by emitting green fluorescence, thus making it feasible to use such animals in a passive transfer model for EAE. When MOG-sensitized splenic lymphocytes from GFP-Tg mice were adoptively transferred to irradiated, syngeneic C57BL/6 and RAG-1(-/-)mice, typical symptoms of EAE developed. Analysis of the reconstituted mice with EAE revealed prominent infiltration of fluorescing (GFP+), CD4+ T cells into the central nervous system (CNS). Real-time confocal imaging revealed these cells in the spinal cords and brains of recipient mice. This infiltration was also confirmed by anti-GFP monoclonal antibodies. Furthermore, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) evaluation indicated that the infiltrating GFP+, CD4+ T cells exclusively produced T helper type 1 (Th1) cytokines, especially interferon-gamma (IFN-gamma). These results clearly show that MOG-specific CD4+ T cells preferentially invade into the CNS and mediate the development of EAE by producing Th1-biased cytokines.
Yura
M
M
Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Takahashi
I
I
Serada
M
M
Koshio
T
T
Nakagami
K
K
Yuki
Y
Y
Kiyono
H
H
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000737:chemistry / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000276:immunology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D000954:Antigens, Surface; D016207:Cytokines; D008164:Luminescent Proteins; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D049452:Green Fluorescent Proteins