ANALYSIS OF TYPE-1 AND TYPE-2 T-CELLS IN SYNOVIAL-FLUID AND PERIPHERAL-BLOOD OF PATIENTS WITH RHEUMATOID-ARTHRITIS

Objective, It has been reported that CD4+ helper T cells play an impor tant role in the pathogenesis of rheumatoid arthritis (RA). We evaluat ed the presence of intracellular cytokines interleukin 4 (IL-4) and in terferon-gamma (IFN-gamma) produced by CD4+ and CD8+ T cells in the sy novial fluid and peripheral blood of patients with RA at the single ce ll level. Methods, We used 3 color flow cytometric analysis. Synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) were stimulated with phorbol myristate acetate (PMA) and calciu m ionophore. The stimulated SFMC and PBMC were triple stained with con jugated mononuclear antibodies (Mab) against cytokines and surface ant igens after fixation and permeabilization with a saponine buffer solut ion. The cells were analyzed for intracellular cytokines (IFN-gamma, I L-4) and surface antigens (CD3, CD4, CD8) using a flow cytometer. Resu lts, The CD4/CD8 ratio was significantly lower in SFMC than in PBMC. T he positive rates of IFN-gamma producing cells among CD4+ T cells were significantly higher than those of IL-4 producing cells in both the S FMC and the PBMC of patients with active RA. In the SF of these patien ts, we also found CD8+ T cells that produce IL-4 alone, or both IL-4 a nd IFN-gamma, Conclusion. In the SF of patients with RA, CD4+ type 1 T cells, which may infiltrate into the synovium and cause pathogenic im mune responses in the tissue, are predominant. We believe this cell ty pe also induces migration and activation of CD8+ type 2 T cells into t he active site of inflammation, which appears to downregulate the acti vity of CD4+ type 1 T cells, modulating the excess immune response.