TCR CD3 COMPLEX-MEDIATED SIGNAL-TRANSDUCTION PATHWAY IN T-CELLS AND T-CELL LINES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS/

We studied the TCR/CD3 complex-mediated signal transduction pathway in freshly isolated T cells and T cell lines from patients with systemic lupus erythematosus (SLE). The peak and 5-min anti-CD3 mAb-mediated f ree intracytoplasmic Ca2+ concentration ([Ca2+](i)) increase was stati stically significant higher in fresh T cells from SLE patients than in control T cells. Increased CD3-mediated [Ca2+](i) responses were obse rved in T cells from patients with SLE but not in T cells from other r heumatic diseases. Furthermore, significantly increased CD3-mediated [ Ca2+](i) responses were observed in T cell lines from SLE patients but not from controls. Although the [Ca2+](i) response did not correlate with the global SLE disease activity or individual clinical manifestat ions, it was significantly higher in the group of patients who were no t on treatment. Both CD4(+) and CD8(+) T cell subsets from peripheral blood cells and T cell lines displayed higher CD3-mediated [Ca2+](i) r esponses than their normal counterparts. The peak of the response occu rred earlier in the patient than in the normal group. The amount of Ca 2+ that was released from the intracellular stores was higher in lupus than control T cells. The TCR/CD3-induced production of inositol phos phate metabolites in SLE cells was comparable with controls. The sarco plasmic and endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin-i nduced [Ca2+](i) response was similar in both SLE and normal T cells. Our experiments demonstrate for the first time a definite abnormality in the early steps of the TCR/CD3-mediated signal transduction pathway in T cells from SLE patients that involves increased release of Ca2from intracellular stores.