Efficacy of peripheral tolerance induced by dendritic cells is dependent on route of delivery.
Previous studies have demonstrated that the route of delivery of dendritic cells (DC) is an important variable in eliciting anti-tumor immunity. In contrast, little is known about different routes of DC administration to influence peripheral tolerance in autoimmune diseases. Here we compared therapeutic effect of splenic IFN-gamma-modified-DC (IFN-gamma-DC) in actively induced experimental allergic encephalomyelitis (EAE) by different routes of DC delivery. Following subcutaneous (s.c.) injection, IFN-gamma-DC effectively suppressed clinical signs of EAE, whereas intravenous (i.v.) injection did not inhibit clinical signs of EAE. Compared to s.c. injection, i.v. injection of IFN-gamma-DC failed to mediate T cell responses, but stimulated anti-MBP antibody production and upregulated pro-inflammatory IL-1beta, IFN-gamma and TNF-alpha as well as RANTES expression which may contribute to the accumulation of inflammatory cells within the central nervous system. These results suggest that the administration route of DC should be considered as an important factor for DC-based immunotherapy in autoimmune diseases.
Zhang
Qing-Hong
QH
Division of Neuroimmunology, NEUROTEC Department, Karolinska Institute, Stockholm, Sweden.
Link
Hans
H
Xiao
Bao-Guo
BG
D000818:Animals; D002455:Cell Division / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D013116:Spinal Cord / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D013997:Time Factors
D018925:Chemokines; D012333:RNA, Messenger; D007371:Interferon-gamma