Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus

Abstract

Objectives To explore the relationships between Fas–FasL-mediated signaling pathway and apoptosis disturbance of T lymphocyte subset in patients with SLE. Methods Flow cytometry was used to determine the percentage of apoptotic lymphocytes and necrotic lymphocytes by AnnexinV–FITC/PI double staining. Cell surface expression rates of Fas, FasL, and intracellular expression rates of activated caspase-3 were evaluated by two-color flow cytometry analysis in peripheral T lymphocyte subsets of SLE patients with inactive disease ( n = 22) and with active disease ( n = 17). The serum concentration of anti-nucleosome antibodies in SLE patients were assayed by ELISA immunoassay methods. Health volunteers ( n = 13) served as controls. Results The percentage of early apoptotic cells was enhanced in patients with active disease ( P = 0.001, vs. control) and in patients with inactive disease ( P = 0.004, vs. control). Compared with health control, the percentage of necrotic cells was significant higher in patients with active disease ( P = 0.001). The percentages of CD4 +T cells expressing Fas ( P = 0.023, vs. control) and FasL ( P = 0.001, vs. control) were increased in patients with active disease. But there were no obvious differences of expression rates of Fas and FasL on T cell subset between two disease groups ( P > 0.05). In patients with active disease the percentage of CD4 +T cells or CD8 +T cells expressing intracellular activated caspase-3 significantly increased compared to inactive disease patients ( P = 0.018, P = 0.027, respectively) and health controls ( P = 0.001, P = 0.001, respectively). The serum concentration of anti-nucleosome antibodies was strikingly higher in patients with active disease ( P = 0.002, vs. patients with inactive disease; P = 0.001, vs. control, respectively), however, the serum concentration of anti-nucleosome antibodies was not obviously different between patients with inactive disease and health control group ( P = 0.473). The percentage of apoptotic cells correlated with the serum concentration of anti-nucleosome antibodies in SLE patients ( r s = 0.350, P = 0.031). Conclusions Apoptosis of T lymphocyte subset in SLE patients increases. CD4 +T cells are a state of active apoptosis. Fas/FasL-mediated apoptotic pathways are especially important for CD4 +T cells undergoing apoptosis in SLE patients with active disease. Increased Fas expression results in a higher susceptibility to Fas-mediated apoptosis, which contributes to the increased levels of intracellular activated caspase-3 and accelerates apoptosis of T lymphocytes. The degree of lymphocytic apoptosis disturbance correlates with the level of anti-nucleosome antibodies in the circulation. Acceleration of lymphocytic apoptosis plays important roles in immune pathologic injury and immune regulation dysfunction.