title: TGF-beta1 inhibits protracted-relapsing experimental autoimmune encephalomyelitis by activating dendritic cells.
abstract: Protracted-relapsing experimental autoimmune encephalomyelitis (PR-EAE) in DA rats is an animal model closely related to multiple sclerosis (MS). Previous studies showed that nasal administration of TGF-beta1 suppressed the development and relapse of PR-EAE clinically and pathologically. Here we demonstrate that this suppressive effect was associated with activation of dendritic cells (DC), showing elevated proliferative response and IFN-gamma and nitric oxide (NO) production by DC. DC derived from TGF-beta1-treated rats with PR-EAE also showed high expression of nitric oxide synthase 2 (NOS2) at both mRNA and protein levels. Apoptotic cells were increased in spleen sections of TGF-beta1-treated rats compared to control rats. In studying mechanisms of apoptosis in TGF-beta1-treated rats, in vitro experiments demonstrated that TGF-beta1-treated DC induced apoptosis of CD4(+)T cells by a NO pathway after co-culture with T cells. These results support the hypothesis that TGF-beta1-induced suppression of PR-EAE is associated with apoptosis of CD4(+)T cells induced by DC-derived NO.
authors.affiliation: Division of Neurology, Units of Experimental Neurology and Neuroimmunology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden.
authors.forename: Y X
authors.initials: YX
authors.lastname: Jin
authors.forename: L Y
authors.initials: LY
authors.lastname: Xu
authors.forename: H
authors.initials: H
authors.lastname: Guo
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: B G
authors.initials: BG
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D009569:Nitric Oxide / Q000276:immunology*; D051381:Rats; D012008:Recurrence; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D007371:Interferon-gamma