International Immunology, Vol. 16, No. 1, pp. 13-22,
January 2004
© 2004 Japanese Society for Immunology
Therapeutic potential of IFN-
-modified dendritic cells in acute and chronic experimental allergic encephalomyelitis
1 Division of Neuroimmunology, Neurotec and 2 MRC, Department of Clinical Neuroscience, Karolinska Institute, 14183 Stockholm, Sweden 3 Institute of Neurology, Fudan University, Shanghai 200433, China
Correspondence to: B.-G. Xiao; E-mail: Bao-guo.Xiao{at}neurotec.ki.se
Transmitting editor: E. Simpson
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-
(IFN--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--DC were injected s.c. Severity of clinical signs of EAE was dramatically inhibited in animals injected with IFN--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--DC triggered an antigen-specific IFN- production, and induced apoptosis of CD4+ T cells possibly through DC expressing indoleamine 2,3-dioxygenase and/or an IFN--dependent pathway. As a result, infiltration of macrophages and CD4+ T cells within the spinal cords was dramatically reduced in animals injected with IFN--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.
Keywords: dendritic cell, experimental allergic encephalomyelitis, IFN-, magnetic resonance imaging, tolerance
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Nakagome, K. Okunishi, M. Imamura, H. Harada, T. Matsumoto, R. Tanaka, J.-i. Miyazaki, K. Yamamoto, and M. Dohi IFN-{gamma} Attenuates Antigen-Induced Overall Immune Response in the Airway As a Th1-Type Immune Regulatory Cytokine J. Immunol., July 1, 2009; 183(1): 209 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Terness, T. Oelert, S. Ehser, J. J. Chuang, I. Lahdou, C. Kleist, F. Velten, G. J. Hammerling, B. Arnold, and G. Opelz Mitomycin C-treated dendritic cells inactivate autoreactive T cells: Toward the development of a tolerogenic vaccine in autoimmune diseases PNAS, November 25, 2008; 105(47): 18442 - 18447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Frasca, M. Nasso, F. Spensieri, G. Fedele, R. Palazzo, F. Malavasi, and C. M. Ausiello IFN-{gamma} Arms Human Dendritic Cells to Perform Multiple Effector Functions J. Immunol., February 1, 2008; 180(3): 1471 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Feunou, S. Vanwetswinkel, F. Gaudray, M. Goldman, P. Matthys, and M. Y. Braun Foxp3+CD25+ T Regulatory Cells Stimulate IFN-{gamma}-Independent CD152-Mediated Activation of Tryptophan Catabolism That Provides Dendritic Cells with Immune Regulatory Activity in Mice Unresponsive to Staphylococcal Enterotoxin B J. Immunol., July 15, 2007; 179(2): 910 - 917. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Raine, P. Zaccone, P. Mastroeni, and A. Cooke Salmonella typhimurium Infection in Nonobese Diabetic Mice Generates Immunomodulatory Dendritic Cells Able to Prevent Type 1 Diabetes J. Immunol., August 15, 2006; 177(4): 2224 - 2233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-M. Huang, X. Liu, K. Steffensen, A. Sanna, G. Arru, M. L. Fois, G. Rosati, S. Sotgiu, and H. Link Immunological heterogeneity of multiple sclerosis in Sardinia and Sweden Multiple Sclerosis, February 1, 2005; 11(1): 16 - 23. [Abstract] [PDF]
|
|
|
|
|
|
F. Fallarino, C. Asselin-Paturel, C. Vacca, R. Bianchi, S. Gizzi, M. C. Fioretti, G. Trinchieri, U. Grohmann, and P. Puccetti Murine Plasmacytoid Dendritic Cells Initiate the Immunosuppressive Pathway of Tryptophan Catabolism in Response to CD200 Receptor Engagement J. Immunol., September 15, 2004; 173(6): 3748 - 3754. [Abstract] [Full Text] [PDF]
|
|