Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine.

Abstract

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-kappaB 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.

• Authors: Igor Popov, Mu Li, Xiufen Zheng, Hongtao San, Xusheng Zhang, Thomas E Ichim, Motohiko Suzuki, Biao Feng, Costin Vladau, Robert Zhong, Bertha Garcia, Gill Strejan, Robert D Inman, Wei-Ping Min
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 8 Issue 5 Pg. R141 ( 2006) ISSN: 1478-6362 [Electronic] England
• PMID: 16911769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type II
• Guanidines
• Immunosuppressive Agents
• LF 150195
• Vaccines

Topics

• Animals
• Arthritis, Experimental (immunology, pathology, prevention & control)
• Autoimmune Diseases (immunology, pathology, prevention & control)
• Cell Differentiation (drug effects, immunology)
• Cell Division (drug effects, immunology)
• Cells, Cultured
• Collagen Type II (immunology)
• Dendritic Cells (cytology, drug effects, immunology)
• Guanidines (pharmacology)
• Immune Tolerance (immunology)
• Immunosuppressive Agents (pharmacology)
• Lymphocyte Culture Test, Mixed
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• T-Lymphocytes (immunology)
• Vaccines (immunology)