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.
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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)
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Chemical References |
- Collagen Type II
- Guanidines
- Immunosuppressive Agents
- LF 150195
- Vaccines
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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)
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