SHIFT TOWARD T HELPER 1 CYTOKINES BY TYPE II COLLAGEN REACTIVE T CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS.

초록

Objective: To investigate the impact of type II collagen(CII) reactive T cells on Th1/Th2 cytokine balance in patients with rheumatoid arthritis(RA). Methods: T cells proliferative responses to bovine CII, were examined in synovial fluid mononuclear cells(SFMC) and peripheral blood mononuclear cells(PBMC) by mixed lymphocyte culture. CII reactive T cell lines were generated from the SFMC and PBMC. Interferon gamma(IFN-g), interleukin-12(IL-12) and interleukin-4(IL-4) were measured by ELISA in the synovial fluids (SF), sera, the culture supernatants of PBMC and SFMC stimulated with CII. Results: The frequency of CII reactive T cells were higher in the PBMC of RA than that in the PBMC of osteoarthritis(OA) and in healthy controls(p<0.001). In RA, CII reactive T cells in SFMC were more prevalent than in PBMC. The mean levels of IFN-g and the ratio of INF-g/IL-4 were significantly higher in the culture supernatants of T cells stimulated with CII and these differences were more prominent in SFMC. Moreover, the levels of IL-12 in the culture supernatants of SFMC and PBMC stimulated with CII were significantly higher than those without CII. T cell responsiveness correlated well with the level of type 1 cytokines of culture supernatants from RA T cells stimulated with CII. In the CII-reactive cell lines, the increased production of IFN-g was consistent with the clonal expansion. Conclusion: CII-reactive T cells are more apparently present in SFMC than that in PBMC and strongly associated with a shift toward type 1 cytokine in the inflammed joints of RA. Our results suggest that a skewing to type 1 cytokines by CII-reactive T cells may play an important pathogenic role in chronic inflammatory process in RA. Disclosure: This work is supported by a grant from the Catholic University of Korea. Arthritis Rheumatism 43(9, suppl):S157, 2000