Research article
Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine
-
* Corresponding author: Wei-Ping Min mweiping@uwo.ca
1 Department of Surgery, Microbiology and Immunology, and Pathology, London Health Science Centre, London, Canada
2 Multi-Organ Transplant Program, London Health Science Centre, London, Canada
3 Immunology and Transplantation, Lawson Health Research Institute, London, Canada
4 Robarts Research Institute, London, Canada
5 Division of Rheumatology, Department of Medicine, Toronto Western Hospital, University Health Network, Toronto, Canada
Arthritis Research & Therapy 2006, 8:R141 doi:10.1186/ar2031
Published: 15 August 2006Abstract
Conventional treatments for autoimmune diseases have relied heavily on nonspecific immune suppressants, which possess a variety of adverse effects without inhibiting the autoimmune process in a specific manner. In the present study we demonstrate the effectiveness of antigen-specific, maturation-resistant, tolerogenic dendritic cells (DC) in suppressing collagen-induced arthritis, a murine model of rheumatoid arthritis. Treatment of DC progenitors with the NF-κB inhibiting agent LF 15-0195 (LF) resulted in a population of tolerogenic DC that are characterized by low expression of MHC class II, CD40, and CD86 molecules, as well as by poor allostimulatory capacity in a mixed leukocyte reaction. Administering LF-treated DC pulsed with keyhole limpet hemocyanin antigen to naïve mice resulted hyporesponsiveness specific for this antigen. Furthermore, administration of LF-treated DC to mice with collagen-induced arthritis resulted in an improved clinical score, in an inhibited antigen-specific T-cell response, and in reduced antibody response to the collagen. The efficacy of LF-treated DC in preventing arthritis was substantiated by histological examination, which revealed a significant decrease in inflammatory cell infiltration in the joints. In conclusion, we demonstrate that in vitro-generated antigen-specific immature DC may have important potential as a tolerogenic vaccine for the treatment of autoimmune arthritis.