| OBJECTIVETo explore the important role of T helper cell subsets in the pathogenesis of rheumatoid arthritis by analysing Th0/Th1/Th2 intracelluar cytokine( γ -IFN and IL-4) secretion patterns in peripheral blood of patients with RA at single -cell level by three color flow cytometry , to investigate the effects of type Ⅱ collagen on the T-helper cell subsets , and to study the mechanism of type Ⅱ collagen in the treatment of rheumatoid arthritis. METHODSSurface antigen(CD3/4/8) of T cells and intracellular cytokine (γ -IFN and IL-4) in peripheral blood from active RA (n=33) and healthy controls(n=16) were assayed by three-color flow cytometry at single-cell level, correlations of the frequency of CD3/CD4/CD8, Th0/Th1/Th2 cell subsets and with ESR,C-RP, PLT and HAQ were analyzed respectively. Meanwhile Th0/Th1/Th2 cell subsets in different groups, such as early RA and chronic RA groups, with bone erosion and without erosion groups, positively of RF and negatively of RF groups were analyzed. In addition , Th0/Th1/Th2 cell subsets of 10 early patients with RA patients were also be detected after treatment with oral type Ⅱ collagen for the does of 90ug/d for 3 months. RESULTS1. Imbalance of Tcell subsets and T-helper cell subsets in patients with RA: CD4+ T cells and the ratio of CD4/CD8 was found significantly higher in peripheral blood of patients with RA than that in the healthy controls whether stimulated with PMA or not, and CD4+T cells were correlated significantly with HAQ, CD8+T cells in peripheral blood of RA patients was higher as compared with healthy controls after stimulatedwith PMA for 2 hours. ThO and Thl cells were significantly decreased in patients with RA as compared with healthy individuals. Although no differences were found in the Th2 subsets and the ratio of Thl/Th2 between the groups, the frequency of Th2 cells was positively correlated with ESR. the ratio of Thl/Th2 was negatively correlated with ESR.2. The imbalance of T-helper subsets was associated with the duration of RA and correlated with disease severity : By comparing with early and chronic RA, we found that early RA patients were predominated in Thl subsets and the ratio of Thl/Th2, while chronic RA were dominated in Th2 subsets. In early RA, Thl subsets were positively correlated with ESR and CRP. in chronic RA, Th2 subsets were positively correlated with ESR. Thl cells and the ratio of Thl/Th2 was significantly increased and Th2 cells were significantly decreased in RA patients without bone erosion as compared with bone destructed . There were no differences in ThO/Thl/Th2 subsets between RF positively and negatively RA groups.3. Effect of oral C II on T-helper cell subsets: Treated with type II collagen for 3 months, CD4+T cells and the ratio of Thl/Th2 was significantly decreased, ThO and Th2 cells was significantly increased as compared with pre- treatment. No differences was found in Thl cells after treatment with C II.CONCLUSIONSCD4+T cell and imbalance of Th cell subset played an important role in the pathogenesis of RA, especially CD4+T cell, is a key position contributed to the development of RA. The patters of Th cell subsets were not stationary in the process of RA, it could be changed with the prolonged of duration of disease.In early RA,Thl cells showed a dominant pattern while in chronic RA, Th2 cells showed a predominantly profile and they all have closly relationship with disease severity.Meanwhile,RA patients have an imbalance of TcO/Tcl/Tc2 in peripheral blood.C II could down-regulated the expression of CD4 on the surface of T lymphocyte of early RA...
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