Characterization of altered calcium signalling in T lymphocytes from patients with rheumatoid arthritis (RA).
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.
Carruthers
D M
DM
Department of Rheumatology, University of Birmingham, UK.
Naylor
W G
WG
Allen
M E
ME
Kitas
G D
GD
Bacon
P A
PA
Young
S P
SP
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*
D017252:CD3 Complex; D010835:Phytohemagglutinins; D002118:Calcium