INCREASED EXPRESSION OF SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE IN PATIENTS WITH RHEUMATOID-ARTHRITIS AND ITS ROLE IN THE REGULATION OF CYTOKINE PRODUCTION IN RHEUMATOID SYNOVIUM

In the present study the expression and function of signaling lymphocy tic activation molecule (SLAM) in lymphocytes from patients with rheum atoid arthritis (RA) were investigated. The expression levels of SLAM were significantly up-regulated on synovial fluid and synovial tissue T cells from patients with RA compared with peripheral blood T cells f rom the same patients or from healthy volunteers. In addition, the exp ression of SLAM on peripheral blood B cells from patients with RA was elevated compared with that in healthy volunteers. SLAM(+) T cells in synovial fluid coexpressed CD45RO and demonstrated decreased expressio n of CD27, indicative of a primed phenotype. In addition, the activati on state of SLAM(+) T cells was enhanced, as judged by increased expre ssion of CD25, CD28, CD69, and CD95 on these cells. Interestingly, SLA M expression on activated CD4(+) and CD8(+) T cells from both patients and healthy individuals could be down-regulated by IL-10, which has b een previously shown to function as an anti-inflammatory molecule in r heumatoid synovium. Furthermore, anti-SLAM mAbs increased the producti on of IL-10, IFN-gamma, and TNF-alpha by in vitro activated synovial f luid mononuclear cells, supporting the idea that signaling through SLA M may play a role in the regulation of synovial inflammation in patien ts with RA. Given the fact that SLAM was recently shown to be a high a ffinity self ligand, our data suggest that synovial T cells may stimul ate their own cytokine production through hemophilic SLAM-SLAM interac tions.