Characterization of altered calcium signalling in T lymphocytes from patients with rheumatoid arthritis (RA)

Abstract

Abnormal function of peripheral blood T lymphocytes is characteristic of RA; diminished proliferation and secretion of cytokines following in vitro mitogen stimulation are observed. We have investigated the calcium flux initiating T cell activation in rheumatoid peripheral blood mononuclear cells (PBMC) to determine whether abnormalities in signalling are also present. We have found that both phytohaemagglutinin (PHA-P)- and anti-CD3-stimulated calcium fluxes were much reduced in the patients’ PBMC compared with controls, with a mean six-fold difference (P < 0·01) in rate of Ca²⁺ flux with PHA-P stimulation. When purified T cells were examined with PHA and CD3 stimulation, a reduction in the peak and plateau [Ca²⁺]_i was observed in RA T cells, but the rate of rise of [Ca²⁺]_i was only reduced in those cells stimulated with PHA. These results suggest that alterations in the initiating signal may underlie the functional T cell abnormalities associated with RA, and that there may be an additional extrinsic influence from non-T cells in the PBMC population.

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