Defective CD3-Mediated Cell Death in Activated T Cells from Patients with Systemic Lupus Erythematosus: Role of Decreased Intracellular TNF-α

Activation-induced cell death (AICD) plays an important role in the regulation of the immune response by eliminating preactivated and potentially autoreactive cells. To elucidate possible abnormalities of AICD in human systemic lupus erythematosus (SLE), we studied AICD in activated T cells from pat...

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Bibliographic Details
Published in:Clinical immunology and immunopathology 1996-12, Vol.81 (3), p.293-302
Main Authors: Kovacs, Birgit, Vassilopoulos, Dimitrios, Vogelgesang, Scott A., Tsokos, George C.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Apoptosis - immunology
Biological and medical sciences
CD3 Complex - physiology
Cell Line
Female
Humans
Intracellular Fluid - immunology
Intracellular Fluid - metabolism
Lupus Erythematosus, Systemic - etiology
Lupus Erythematosus, Systemic - immunology
Lymphocyte Activation
Male
Medical sciences
Middle Aged
Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis
T-Lymphocytes - immunology
Tumor Necrosis Factor-alpha - deficiency
Tumor Necrosis Factor-alpha - physiology
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Summary:Activation-induced cell death (AICD) plays an important role in the regulation of the immune response by eliminating preactivated and potentially autoreactive cells. To elucidate possible abnormalities of AICD in human systemic lupus erythematosus (SLE), we studied AICD in activated T cells from patients with SLE and normal controls. CD3-mediated cell death was determined in short-term T cell lines by flow cytometry using propidium iodide staining and analysis of DNA subdiploid peak populations. It was found to be significantly lower in T cells from SLE patients compared to cells from normal controls. Anti-Fas mAb-mediated cell death was similar in SLE and control cell lines. CD3-mediated AICD could be blocked in control and SLE T cell lines by an IgG anti-Fas mAb. Indirect immunofluorescence analysis showed statistically significantly less intracellular TNF-α in SLE T cells than in control cells. These data show that activated T cells from patients with SLE are relatively resistant to a TCR-mediated death stimulus although they display intact anti-Fas mAb-mediated cell death. Defective antigen-mediated cell death can contribute to increased numbers of activated autoreactive cells in lupus patients.
ISSN:0090-1229
1090-2341
DOI:10.1006/clin.1996.0192