| 1. |
- Dzhambazov, Balik, et al.
(author)
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Therapeutic vaccination of active arthritis with a glycosylated collagen type II peptide in complex with MHC class II molecules
- 2006
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In: Journal of Immunology. - Rockville, MD : American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 176, s. 1525-33
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Journal article (peer-reviewed)abstract
- In both collagen-induced arthritis (CIA) and rheumatoid arthritis, T cells recognize a galactosylated peptide from type II collagen (CII). In this study, we demonstrate that the CII259-273 peptide, galactosylated at lysine 264, in complex with Aq molecules prevented development of CIA in mice and ameliorated chronic relapsing disease. In contrast, nonglycosylated CII259-273/Aq complexes had no such effect. CIA dependent on other MHC class II molecules (Ar/Er) was also down-regulated, indicating a bystander vaccination effect. T cells could transfer the amelioration of CIA, showing that the protection is an active process. Thus, a complex between MHC class II molecules and a posttranslationally modified peptide offers a new possibility for treatment of chronically active autoimmune inflammation such as rheumatoid arthritis. © 2006 by The American Association of Immunologists, Inc.
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| 2. |
- Li, Jinan, et al.
(author)
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The plasminogen activator/plasmin system is essential for development of the joint inflammatory phase of collagen type II-induced arthritis.
- 2005
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In: American Journal of Pathology. - New York : Elsevier. - 0002-9440 .- 1525-2191. ; 166:3, s. 783-792
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Journal article (peer-reviewed)abstract
- The plasminogen activator (PA) system has been proposed to have important roles in rheumatoid arthritis. Here we have used the autoimmune collagen type II (CII)-induced arthritis (CIA) model and mice deficient for urokinase-type PA (uPA) or plasminogen to investigate the role of the PA system for development of arthritis. Our data revealed that uPA-deficient mice have a lower severity and incidence of CIA than wild-type mice. Furthermore, although >80% of wild-type control mice developed CIA, we found that none of the 50 plasminogen-deficient littermates that were tested developed CIA within a 40-day period. Antibody generation after CII immunization as well as the binding of labeled anti-CII antibodies to the surface of cartilage were similar in wild-type and plasminogen-deficient mice. No sign of inflammation was seen when plasminogen-deficient mice were injected with a mixture of monoclonal antibodies against CII. However, after daily injections of human plasminogen, these mice developed arthritis within 5 days. Our finding that infiltration of inflammatory cells into the synovial joints was impaired in plasminogen-deficient mice suggests that uPA and plasminogen are important mediators of joint inflammation. Active plasmin is therefore essential for the induction of pathological inflammatory joint destruction in CIA.
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