FUNCTIONAL-ANALYSIS OF SYNOVIAL-FLUID AND PERIPHERAL-BLOOD T-CELLS FROM PATIENTS WITH RHEUMATOID-ARTHRITIS

Rheumatoid arthritis is a T cell-mediated autoimmune disease. The lack of knowledge of the involved target antigens severely hampers researc h on relevant T cells in patients. Here we describe the functional ana lysis of freshly isolated T cells from the peripheral blood and the si te of the lesion (synovial fluid or synovial membrane) of patients wit h rheumatoid arthritis. Healthy donors and osteoarthritis patients ser ved as controls. Using various polyclonal stimuli, we analyzed CD4(+) T cells with respect to proliferation and their ability to produce lym phokines. Our data show that lesion-derived CD4(+) T cells of patients with rheumatoid arthritis are severely defective in proliferation and lymphokine (interleukin-2, interleukin-4, tumor necrosis factor-alpha , interferon-gamma) production. This activation defect was most pronou nced at lower cell densities and was present in both synovial fluid de rived and synovial membrane derived CD4(+) T cells of all patients tes ted. No difference was found between responses of synovial fluid deriv ed CD4(+) T cells from osteoarthritis patients and those observed with peripheral blood derived T cells from all groups. The observed defect in lesion-derived CD4(+) T cells from rheumatoid arthritis patients w as not due to the effect of inflammatory factors in the synovial fluid because preincubation with synovial fluid could not induce a similar defect in control T cells. Together, our data show a rheumatoid arthri tis specific, general defect in the activation of lesion-derived CD4() T cells.