Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus.
OBJECTIVE
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.
Xue
Chen
C
Division of clinical immunological laboratory, Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, China [corrected]
Lan-Lan
Wang
W
Bei
Cai
C
Jie
Chen
C
Wei-Hua
Feng
F
D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D048069:Tumor Necrosis Factors / Q000378:metabolism / Q000502:physiology*; D019014:fas Receptor
C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D048069:Tumor Necrosis Factors; D019014:fas Receptor; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases