title: Therapeutic potential of IFN-gamma-modified dendritic cells in acute and chronic experimental allergic encephalomyelitis.
abstract: Dendritic cells (DC) are antigen-presenting cells specialized to regulate immune responses. DC not only control immunity, but also maintain tolerance to self-antigens-two complementary functions that would ensure the integrity of the organism in an environment full of pathogens. Here we report that splenic DC that had been exposed in vitro to IFN-gamma (IFN-gamma-DC) exhibit therapeutic potential on acute experimental allergic encephalomyelitis (EAE) in Lewis rats, and on chronic-relapsing EAE in B6 and SJL/J mice. During incipient EAE [day 5 post-immunization (p.i.) in rats, day 7 p.i. in mice], IFN-gamma-DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN-gamma-DC, showing normal magnetic resonance imaging (MRI) of the spinal cord and brain. In contrast, the EAE rats receiving PBS or naive DC had severe clinical signs with multiple and extensive MRI lesions in the spinal cord and brain. IFN-gamma-DC triggered an antigen-specific IFN-gamma production, and induced apoptosis of CD4(+) T cells possibly through DC expressing indoleamine 2,3-dioxygenase and/or an IFN-gamma-dependent pathway. As a result, infiltration of macrophages and CD4(+) T cells within the spinal cords was dramatically reduced in animals injected with IFN-gamma-DC as compared to animals injected with PBS or naive DC. This approach may represent a novel possibility of individualized immunotherapy using autologous, in vitro modified DC as a complement to conventional therapy in multiple sclerosis and other diseases with an autoimmune background.
authors.affiliation: Division of Neuroimmunology, Neurotec and MRC, Department of Clinical Neuroscience, Karolinska Institute, 14183 Stockholm, Sweden. Bao-guo.Xiao@neurotec.ki.se
authors.forename: Bao-Guo
authors.initials: BG
authors.lastname: Xiao
authors.forename: Xing-Chen
authors.initials: XC
authors.lastname: Wu
authors.forename: Jian-She
authors.initials: JS
authors.lastname: Yang
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Xu
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Yu-Min
authors.initials: YM
authors.lastname: Huang
authors.forename: Borje
authors.initials: B
authors.lastname: Bjelke
authors.forename: Hans
authors.initials: H
authors.lastname: Link
mesh_terms: D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology*; D002908:Chronic Disease; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000637:transplantation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D051381:Rats
chemical_list: D007371:Interferon-gamma