Although large numbers of T cells infiltrate the synovium of patients with rheumatoid arthritis (RA), the responses of these cells, as present in the blood and synovial fluid (SF), to exogenous interleukin-2 (IL-2) and their production of IL-2 are diminished. To investigate this functional defect, RA SF were examined for the presence of inhibitors of IL-1 and IL-2. A factor was found which inhibited the IL-&induced proliferation of mitogen-stimulated human T cells and the IL-1-induced proliferation of C3H/Hej mouse thymocytes, but not IL-1-induced fibroblast proliferation. On AcA 54 Ultrogel filtration, the inhibitory activity resided in a fraction with an apparent molecular weight of >70 kd and a major PI of 6.8. The inhibitory effect of RA SF on lymphocyte proliferation was partially corrected with IL-2, but not with IL-1. In the presence of RA SF, normal lymphocytes showed not only a decreased response to exogenous IL-2, but also a decreased production of IL-2. The presence of an inhibitor of IL-2 in RA
. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled antiimmunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M.The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When
The effects of four inflammatory cytokines, IL-1, TNF, IFN-gamma, and IL-6, were assessed on the following functions of human vascular endothelial cells (EC) in culture: expression of procoagulant activity (PCA), endothelial cell-associated thrombomodulin (TM), and IL-6 production. Both IL-1 and TNF induced PCA, reduced TM, and induced IL-6 production in a dose-dependent manner. IFN-gamma had a weak but significant reducing effect on TM and an inducing effect on IL-6 production, while it had no effect on PCA expression. IFN-gamma, however, when added in combination with either IL-1 or TNF, modulated the effects of these cytokines; INF-gamma inhibited the PCA expression and enhanced the reduction of TM and the production of IL-6, which were induced by either IL-1 or TNF. In contrast, IL-6 had no significant effect on the EC functions studied. These results suggest that both IL-1 and TNF are the major cytokines affecting the EC functions that determine the association between the coagulation and the inflammatory response, and that IFN-gamma affects this phenomenon predominantly through the modification of the effects of these cytokines.
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