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

Arthritis Res Ther. 2006;8(5):R141. doi: 10.1186/ar2031.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / prevention & control
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Division / drug effects
  • Cell Division / immunology
  • Cells, Cultured
  • Collagen Type II / immunology
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / 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*


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