SUMMARYMinocycHne has been shown to have an anti-inflammatory effect in patients with rhetimatoid arthritis (RA). Since there is evidence thai RA is a T cell-mediated disease, we investigated Ihe efl'ect of minocycline on human T cell clones derived from the synovium of an RA patient. The T cells, when activated via the T cell receptor {TCR)/CD3 complex, were suppressed functioniiUy by minocyciine, resulting in a dose-dependent inhibition of T eell proliferation and reduction in production of lL-2. inlerferon-gamma (IFN-7) and tumour necrosis faetor-alpha (TNF-Q). Besides an inhibition of IL-2 production, mitiocycline exerted its effect on T cell proliferation by induction of a decreased IL-2 responsiveness. We showed that the ehelating capacity of minocycline plays a crucial role in the inhibitory effect on T eell function, since the inhibitory elTecl on T cell proliferation could be annulled hy addition of exogenous Ca^^. However, minocycline did nol markedly influence the typical TCR/CD3-induced intracellular Ca^* mobilization. Taken together. Ihe results elearly indicate that minocycline has immunomodulating effects on human T cells.
A prerequisite for comparative histology of synovial tissue by means of biopsies is insight into the distribution of a marker under study. This investigation focuses on the variation in the presence of T cells and signs of T-cell activation within the rheumatoid joint. For this purpose, multiple slides from several pieces of synovial tissue from different parts of a joint were stained and scored for the expression of CD3, CD25, HLA-DR, Ki67 and interferon-gamma. The variation in scores for the presence of T cells and markers of activation was more pronounced in slides prepared from different pieces of tissue than in slides from one piece of tissue. Based on multiple analysis of variance, methods are suggested to establish a reliable overall score for the expression of a certain marker within a joint. Following validation, such methods may prove to be useful by allowing semiquantitative histology of synovial tissue for studies on arthritis.
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