title: 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.
authors.affiliation: Department of Rheumatology, University of Birmingham, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Carruthers
authors.forename: W G
authors.initials: WG
authors.lastname: Naylor
authors.forename: M E
authors.initials: ME
authors.lastname: Allen
authors.forename: G D
authors.initials: GD
authors.lastname: Kitas
authors.forename: P A
authors.initials: PA
authors.lastname: Bacon
authors.forename: S P
authors.initials: SP
authors.lastname: Young
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D017252:CD3 Complex / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D017252:CD3 Complex; D010835:Phytohemagglutinins; D002118:Calcium