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SUMMARY: T cells implicated in chronic inflammatory diseases such as RA respond weakly when stimulated in vitro with mitogen or antigen. The mechanism behind this hyporesponsiveness is unclear, but a depressed expression of the T cell receptor (TCR)-associated CD3[zeta] chain has been suggested. In the present work we describe a low expression of CD3[zeta] in synovial fluid (SF) T cells from RA patients compared with peripheral blood (PB) T cells, but no difference in CD3[zeta] expression between RA and healthy control PB T cells. In vitro studies demonstrated that granulocytes but not SF macrophages are able to down-regulate the expression of CD3[zeta]. Through stimulation with anti-CD3 antibodies we demonstrated that the TCR-dependent proliferative response was decreased in SF T cells compared with PB T cells. Stimulation with phorbol ester and ionomycin also resulted in a low proliferative response of SF T cells, indicating that both signal transduction through the TCR (stimulation with anti-CD3) and events further downstream in the signalling pathways (stimulation with phorbol ester and ionomycin) are affected. A similar depression of T cell activity was observed when induction of IL-2 and IL-4 was measured. However, SF T cells were not defective in the induction of interferon-gamma (IFN-[gamma]) when stimulated with phorbol myristate acetate (PMA)/ionomycin, in contrast to the diminished IFN-[gamma] response observed after stimulation with anti-CD3. This indicates that the hyporesponsiveness of SF T cells can not be generalized to all T cell functions. The differential response to external stimuli is likely to be of importance for the capacity of SF T cells to influence inflammatory reactions.

(C) 2000 Blackwell Science Ltd.