Shift toward T helper 1 cytokines by type II collagen-reactive T cells in patients with rheumatoid arthritis

Objective. To investigate the impact of type II collagen (CII)-reactive T c ells on the Th1/Th2 cytokine balance in patients with rheumatoid arthritis (RA). Methods. T cell proliferative responses to bovine CII were examined in syno vial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) by mixed lymphocyte culture. CII-reactive T cell lines were generate d from the SFMC and PBMC. Interferon-gamma (IFN gamma), interleukin-12 (IL- 12), and IL-4 were measured by enzyme-linked immunosorbent assay in the SF, sera, and culture supernatants of PBMC and SFMC that had been stimulated w ith CII. Results. The frequency of CII-reactive T cells was higher in the PBMC from RA patients than in that from osteoarthritis patients and healthy control s ubjects. In RA patients, CII-reactive T cells were more prevalent in SFMC t han in PBMC. The mean level of IFN gamma and the ratio of IFN gamma to IL-4 were significantly higher in the culture supernatants of T cells stimulate d with CII; these differences were more prominent in SFMC. Levels of IL-12 in the culture supernatants of SFMC and PBMC stimulated with CII were signi ficantly higher than those in unstimulated supernatants. T cell responsiven ess correlated well with the level of type I cytokines in culture supernata nts from RA T cells stimulated with CII. In the CII-reactive cell lines, th e increased production of IFN gamma was consistent with clonal expansion. Conclusion. CII-reactive T cells are more abundant in SFMC than in PBMC and are strongly associated with a shift toward Th1 cytokine in the inflamed j oints of RA patients. Our results suggest that a skewing toward type 1 cyto kines by CII-reactive T cells may play an important role in the chronic inf lammatory process of RA.