| Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by a chronic inflammation of the synovial membrane which is associated with destruction of cartilage and bone. It is a common human autoimmune disease with a prevalence of about 0.3 % among adults in our country. The pathogenesis is not completely understood, Conventional therapies suppress the immune system nonspecifically and are associated with significant side effects, including infections. Collagen-induced arthritis (CIA)is a tissuespecific autoimmune disease that develops in susceptible animals when they are immunized with type II collagen (C II ).It is characterized by inflammation of synovial joints and possesses many characteristics of human rheumatoid arthritis (RA). By studying on type II collagen-specific cellular and humoral immune reaction in CIA provides a new research clue for CIA and RA pathogenesis and therapy.An antigen-driven autoimmune process is proposed to mediated the joint pathology.Type II collagen(C II),which is one of the major components of articular cartilage and provides the tensile strength of this tissue, is a signification autoantigen associated with the development and therapy of RA. Autoantibodies to CII have been detected in the serum of RA patients.The precise mechanisms whereby immunization with CII leads to a chronic arthritis are not known; however, there is considerable evidence implicatingCII -specific CD4+T cells as the primary mediators of disease induction and complement-fixing anti-C II antibody (Ab) production as the major immune mechanism leading to the local chronic inflammatory response. An important role of CD4+T cells in CIA pathogenesis is implied by the fact that disease susceptibility is restricted to mice that possess certain MHC class II alleles (H-2q and H-2r)There is considerable evidence to suggest that CIA is a Thl-mediated inflammatory disease. However, especially Th2-associated Abs, throughout the course of disease implies that both Thl and Th2 responses are probably involved in modulating arthritis. This is further supported by the identification of complement-fixing Abs on the surface of carticular cartilage, the successful transfer of arthritis by polyclonal Abs purified from the sera of arthritic mice, and the induction of arthritis using a selective combination of mAbs specifically against CII. MHC class II genes in the H-2 region profoundly influence the susceptibility to disease, whereas non-MHC genes exert additional influence. It is generally believed that Mice of the H-2q(DBA/l,Dl) background are highly susceptible to disease whereas mice of the H-2b(C57BL/6,B6)background are resistant. To confirm the importance of genetic background of these two strains in development of CIA and study the immunological pathogenesis of CIA, we systematically analyzed T and B cell immune responses in B6 mice, compared to DBA/1 mice, following immunization with chicken type II collagen(CH).1. The both strains were immunized with emulsified chicken type II collagen(C II) in complete Freund's adjuvant by intradermal injection to induce the mice model of collagen-induce arthritis(CIA).2. The lymphocytes were obtained from spleen of CIA mice killed at 19 days of initial immunization and 7 days, 28 days of booster immunization, and the type II collagen reactive T cells were stimulated by CII in vitro. The proliferation response and phenotype were analyzed by BrdU incorporation and fluorescence-activated cell sorter(FACS);Intracellularcytokines(IFN-y, IL-4)and surface antigen(CD4)of T cells in the peripheral blood of CIA mice were assayed by FACS.3. Anti-CII antibody in serum was assayed by Enzyme-linked immunoadsordent assay (ELISA)at different timepoints after immunization(7,14,21,28,35,42,and 49days); The frequency of IgG anti-CC II antibody-forming spleen cells was measured with an enzyme-linked immunospot assay (ELISPOT) in nitrocellulose-bottomed 96-well plates.4. To investigate the relationship between HLA-DRJ31 allele and the collagen-specific immune reaction in RA, the HLA-DR4 group and it's subtypes HLA-DR01 alleles were studied using "high resolution" PCR-SSP DRpl*04 typing techniques.Results:1. Most DBA/1 mice (18 of 20, 90%) developed progressive disease, with a mean arthritis score of (7.82 ± 1.74), whereas a smaller fraction of B6 mice (14 of 20, 70%) developed visible arthritis, with a significantly lower mean arthritis score of (4.0 ± 1.63)These results confirm the importance of the H-2 region in the development of CIA. Joints from DBA/1 J and B6 with arthritis had similar histological changes.2. In the test, we found that the representation of the Thl cytokine(IFN-y)in the peripheral blood of CIA mice is significantly higher than control groups( P<0.0\ );But a similar representation was observed in the peripheral blood of CIA mice at different timepoints after immunization; In vitro, the frequency of BrdU+ cells in CD4+ T cells stimulated by CII were significantly higher than those of control group(/> |
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