EXPRESSION OF FUNCTIONAL B7 AND CTLA4 ON RHEUMATOID SYNOVIAL T-CELLS

To assess the role of B7, CTLA4, and CD28 in the pathogenesis of chron ic synovitis we analyzed the expression and function of these cell sur face molecules in patients with rheumatoid arthritis, osteoarthritis, and psoriatic arthritis, and in normal controls. Immunoperoxidase stai ning of rheumatoid synovial membranes showed reactivity of 30% of T ce lls with anti-B7 mAb, in contrast to osteoarthritic and normal synovia l membranes, in which no such staining was seen. In addition, rheumato id synovial Fluid T cells were positive by flow cytometric analysis fo r B7 (mean 20%, range 0 to 96%), as measured by staining with anti-B7 mAb or the CTLA4 Ig fusion protein, whereas no B7 expression was detec ted on peripheral blood T cells (mean 1%). To analyze the functional i mportance of B7 expressed on synovial fluid T cells, we used these cel ls as stimulator cells in primary allogeneic MLC. Purified synovial fl uid T cells were far stronger stimulator cells compared with paired pe ripheral blood T cells and resulted in a fivefold greater increase in allogeneic T cell proliferation. Furthermore, the proliferation induce d by purified synovial T cells was markedly inhibited by addition of t he CTLA4 Ig fusion protein (77%). Moreover, anti-B7 mAb (37%), anti-CT LA4 mAb (33%), and Fab fragments of anti-CD28 mAb (52%) partially inhi bited the primary MLC. The expression of functional B7, together with the increased expression of MHC class II molecules, indicates that syn ovial T cells may serve as functional APCs and may be capable of autoc rine stimulation via the CD28 activation pathway.