Some Cellular Aspects of Chronic Inflammation in Joint Disease

We have examined the nature of some mononuclear cells from inflamed synovial membranes of patients with rheumatoid arthritis. It was found that cells which remained in the supernatant medium after overnight culture of trypsinized tissue contained a variable number of lymphocytes which were shown to be T cells by rosetting and mitogen response. This suggests a source of T cell lymphokines with an effect on macrophages and thus a role in the maintenance of inflammation. Another role for mononuclear cells is suggest by the cytotoxicity of blood mononuclear cells directed against cultured synovial cells. This was found to occur in an autologous system using fibroblasts from rheumatoid synovium, but was not specific for rheumatoid arthritis. Stimulatory factors from rheumatoid joint effusion macrophages for blood lymphocytes were sought, but although blast transformation occurred, the results were equivocal. In this communication we set out to examine the nature of lymphoid cells in the synovial membrane and the role which they may play in the pathogenesis of chronic inflammation. We also briefly consider cell-mediated mechanisms of tissue injury. Since an active role of lymphoid cells pre-supposes the presence of an agent or agents which serve to stimulate them, we also report some recent attempts to find evidence for this. One of the striking histological features of the inflamed synovial tissue in rheumatoid arthritis, but also in some other forms of chronic arthritis, is the presence of lymphocytes and plasma cells. Immunofluorescent studies and organ culture studies have shown the presence and synthesis of immunoglobulins, predominantly the domain of plasma cells. The production of immunoglobulins, formation of complexes and activation of complement is a major factor in pathogenesis, but lymphocytes may also have a direct role through the production of lymphokines. Until recently these substances have been attributed to T lymphocytes, but Rocklin et al. (1) have recently shown that B cells may also be involved in certain experimental circumstances. The availability of synovectomy specimens from patients with rheumatoid arthritis has enabled us to examine the nature of lymphoid cells from synovial membranes. (This part of the work is reported fully elsewhere.