SYNOVIAL MONONUCLEAR-CELLS CONSIST WITH T-CELLS WHICH PRODUCE HIGH-LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA

To determine whether synovial mononuclear cells include a population o f tumor necrosis factor alpha-producing T cells, we measured tumor nec rosis alpha levels in culture supernatants of synovial mononuclear cel ls by ELISA and analyzed tumor necrosis or mRNA-positive cell frequenc ies. There were no significant differences in the spontaneous levels o f TNF alpha between synovial mononuclear cells and peripheral mononucl ear cells. The frequency of tumor necrosis factor alpha mRNA-positive cells in synovial mononuclear cells was higher than that of peripheral mononuclear cells. When stimulated with a superantigen, mononuclear c ells from the synovial fluid of rheumatoid arthritis patients showed h igher levels of tumor necrosis factor alpha production (1,035+/-817 pg /ml) than did mononuclear cells from their peripheral blood (236+/-180 pg/ml). In addition, we observed that a few T cell clones were resist ant to superantigenic restimulation in vitro. We conclude that when th ese types of T cells persist in the synovium, they play a role in the development of rheumatoid arthritis via a mechanism involving tumor ne crosis factor alpha production.