TCR/CD3 complex-mediated signal transduction pathway in T cells and T cell lines from patients with systemic lupus erythematosus.

Abstract

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.

• Authors: D Vassilopoulos, B Kovacs, G C Tsokos
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 155 Issue 4 Pg. 2269-81 (Aug 15 1995) ISSN: 0022-1767 [Print] United States
• PMID: 7636273 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Receptor-CD3 Complex, Antigen, T-Cell
• Terpenes
• Thapsigargin
• Inositol 1,4,5-Trisphosphate
• Calcium

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (immunology)
• Calcium (metabolism)
• Cell Line
• Female
• Humans
• Inositol 1,4,5-Trisphosphate (biosynthesis)
• Lupus Erythematosus, Systemic (metabolism)
• Male
• Middle Aged
• Receptor-CD3 Complex, Antigen, T-Cell (physiology)
• Signal Transduction
• T-Lymphocytes (metabolism)
• Terpenes (pharmacology)
• Thapsigargin