Potent adjuvant effect by anti-CD40 in collagen-induced arthritis. Enhanced disease is accompanied by increased production of collagen type-II reactive IgG2a and IFN-gamma.
Collagen type II-induced arthritis (CIA) is an experimental model of rheumatoid arthritis, an autoimmune inflammatory disease of the peripheral joints in humans. CD40 interaction with its ligand CD154 (CD40L) has been shown to be an obligatory step in the initiation of autoimmune disease in several animal models. In this study we report on the effect of CD40 stimulation in CIA induced by immunization with type II collagen (CII) in CFA or IFA. We found that the administration of stimulatory anti-CD40 mAb resulted in earlier onset and more severe disease in IFA-CII-immunized mice. The mAb treatment resulted in markedly elevated titers of CII-specific IgG2a antibodies whereas CII-specific IgG1 titers were unaffected. Draining lymph node cell cultures from mice treated with anti-CD40 exhibited significantly increased IFN-gamma production compared to cultures from control antibody-treated mice. In conclusion, our results indicate that the level of CD40 activation during the induction of an autoimmune response may determine the severity of the resulting disease.
Tellander
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AC
Active Biotech Research AB, Lund, Sweden. annamaria.tellander@activebiotech.com
Michaëlsson
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Brunmark
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Andersson
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M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D000918:Antibody Specificity; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism*; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000276:immunology; D051940:B7-2 Antigen; D019013:CD40 Antigens / Q000096:biosynthesis / Q000276:immunology*; D002417:Cattle; D003094:Collagen / Q000276:immunology*; D005620:Freund's Adjuvant / Q000494:pharmacology; D007114:Immunization; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis*; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; C497965:Cd86 protein, mouse; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D003094:Collagen; D005620:Freund's Adjuvant