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Peripheral blood lymphocytes (PBL) and synovial fluid lymphocytes ( SFL ) of patients with rheumatoid arthritis (RA) were examined with monoclonal antibodies, with coated ox red blood cells for the expression of Fc receptors for IgG or IgM (T mu and T gamma cells), and incubated for the demonstration of alpha- naphtyl acetate esterase and acid phosphatase. Equal percentages of OKT4 and OKT8 PBL were found in clinically active and inactive RA patients, and in healthy controls, but decreased percentages of OKT4 and increased percentages of OKT8-positive lymphocytes were found among the SFL . The percentages of T mu and T gamma cells, the presence of HLA-DR membrane antigens on T lymphocytes as well as the staining pattern for the enzymes revealed that SFL of patients with RA were highly activated, compared to PBL of RA patients and healthy controls. It can be concluded from this study that a single determination of OKT4 and OKT8-positive lymphocytes in the peripheral blood of RA patients has no predictive value for disease activity. However, the results of the experiments on T lymphocyte-activation clearly showed preferential activation of SFL compared to PBL, indicating that activation of lymphocytes occurs at the site of inflammation.
Peripheral blood lymphocytes (PBL) and synovial fluid lymphocytes ( SFL ) of patients with rheumatoid arthritis (RA) were examined with monoclonal antibodies, with coated ox red blood cells for the expression of Fc receptors for IgG or IgM (T mu and T gamma cells), and incubated for the demonstration of alpha- naphtyl acetate esterase and acid phosphatase. Equal percentages of OKT4 and OKT8 PBL were found in clinically active and inactive RA patients, and in healthy controls, but decreased percentages of OKT4 and increased percentages of OKT8-positive lymphocytes were found among the SFL . The percentages of T mu and T gamma cells, the presence of HLA-DR membrane antigens on T lymphocytes as well as the staining pattern for the enzymes revealed that SFL of patients with RA were highly activated, compared to PBL of RA patients and healthy controls. It can be concluded from this study that a single determination of OKT4 and OKT8-positive lymphocytes in the peripheral blood of RA patients has no predictive value for disease activity. However, the results of the experiments on T lymphocyte-activation clearly showed preferential activation of SFL compared to PBL, indicating that activation of lymphocytes occurs at the site of inflammation.
Gold salts in vitro modulate lymphocyte proliferation to mitogens and antigens and macrophage phagocytosis. These effects are not confined to gold salts; D-penicillamine and chloroquine as well as some of the non-steroidal anti-inflammatory drugs (NSAIDs) have in vivo immunoregulatory effects. Peripheral blood mononuclear cells during treatment with Myocrisin (gold sodium thiomalate, GSTM) show changes that differ from in vitro effects and are related to therapeutic response rather than GSTM administration. This discrepancy between in vitro and ex vivo responses prompted us to measure cellular functions during auranofin therapy. Twenty-nine patients with rheumatoid arthritis took part in a placebo-controlled trial of auranofin. We examined the spontaneous immunoglobulin (IgG and IgM) and IgM rheumatoid factor (IgM RF) production by cultured mononuclear cells, lymphocyte transformation to concanavalin A and macrophage phagocytosis of Candida albicans. There was a significant fall in IgG synthesis (p less than 0.005) and IgM RF synthesis (p less than 0.005) over the first 4 months of treatment, whereas in the control group there were no significant changes. There was no significant change in IgM production. In the auranofin-treated group the lymphocyte response to concanavalin A fell progressively during 6 months of therapy (at 2 months p less than 0.05, at 4 months p less than 0.01, and at 6 months p less than 0.005). Auranofin therapy had variable effects on monocyte phagocytosis of C. albicans. Therefore, in contrast to GSTM, auranofin suppressed both in vitro and ex vivo lymphocyte functions. This effect is probably related to the direct effect of auranofin on lymphocyte membranes.
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