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 free intracytoplasmic Ca2+ concentration ([Ca2+]i) increase was statistically significant higher in fresh T cells from SLE patients than in control T cells. Increased CD3-mediated [Ca2+]i responses were observed in T cells from patients with SLE but not in T cells from other rheumatic 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 manifestations, it was significantly higher in the group of patients who were not on treatment. Both CD4+ and CD8+ T cell subsets from peripheral blood cells and T cell lines displayed higher CD3-mediated [Ca2+]i responses than their normal counterparts. The peak of the response occurred earlier in the patient than in the normal group. The amount of Ca2+ that was released from the intracellular stores was higher in lupus than control T cells. The TCR/CD3-induced production of inositol phosphate metabolites in SLE cells was comparable with controls. The sarcoplasmic and endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin-induced [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 Ca2+ from intracellular stores.
Vassilopoulos
D
D
Department of Clinical Investigation, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Kovacs
B
B
Tsokos
G C
GC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism*; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D000911:Antibodies, Monoclonal; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D013729:Terpenes; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium