Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine.
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.
Popov
Igor
I
Department of Surgery, London Health Science Centre, London, Canada.
Li
Mu
M
Zheng
Xiufen
X
San
Hongtao
H
Zhang
Xusheng
X
Ichim
Thomas E
TE
Suzuki
Motohiko
M
Feng
Biao
B
Vladau
Costin
C
Zhong
Robert
R
Garcia
Bertha
B
Strejan
Gill
G
Inman
Robert D
RD
Min
Wei-Ping
WP
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006146:Guanidines / Q000494:pharmacology; D007108:Immune Tolerance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology*
D024043:Collagen Type II; D006146:Guanidines; D007166:Immunosuppressive Agents; C434185:LF 150195; D014612:Vaccines