Article: article from journal or magazin.
Oxidized low-density lipoproteins activate CD4+ T cell apoptosis in patients with end-stage renal disease through Fas engagement
Journal of the American Society of Nephrology
In Vitro Journal Article Research Support, Non-U.S. Gov't
Oxidized LDL (oxLDL) are cytotoxic to vascular cells, but their possible toxic action on T cells from patients with ESRD has not been evaluated. oxLDL concentrations were measured and compared in patients who were on long-term hemodialysis (HD), in patients who had ESRD and were on continuous ambulatory peritoneal dialysis, in nondialyzed patients with chronic kidney disease, and in age- and gender-matched control subjects. In parallel, the proliferative capacity of CD69+/CD4+ T cells and their rate of apoptosis, IL-2 expression, and intracellular expression of Bcl-2 and Bax were determined in vitro. The oxLDL concentrations were significantly higher in HD patients (all P = 0.001). Upon phytohemagglutinin stimulation, CD69+/CD4+ T cells from HD patients proliferated significantly less than those from the other patients' group (both P < 0.001). oxLDL but not the native LDL were led to CD69+/CD4+ T cells' program cell death in a dosage- and time-dependent manner through Fas pathway (P = 0.001). Cell surface Fas expression was followed by DNA fragmentation when CD69+/CD4+ T cells from HD patients or control subjects were cultured with oxLDL (200 microg/ml; 31 +/- 3 versus 25 +/- 3%; P = 0.001). In the presence of oxLDL, CD69+/CD4+ T cells from HD patients expressed significantly lower IL-2 levels, which strongly correlated with a decrease in the antiapoptotic Bcl-2 and conversely with an increase in the proapoptotic Bax expression. In conclusion, these data suggest that, in HD patients, exposure of activated CD4+ T cells to oxLDL leads to Fas-mediated apoptosis in association with inhibition of IL-2 expression. Subsequently, this may favor activation of mitochondria-dependent apoptotic pathways, leading to activated CD4+ T cell dysfunction.
Antigens, CD/metabolism Antigens, CD95/*metabolism Antigens, Differentiation, T-Lymphocyte/metabolism Apoptosis/drug effects/physiology CD4-Positive T-Lymphocytes/drug effects/immunology/*metabolism/*pathology Case-Control Studies Cell Proliferation Cell Survival Female Humans Interleukin-2/metabolism Kidney Failure, Chronic/immunology/*metabolism/*pathology Lipids/blood Lipoproteins, LDL/blood/*metabolism/*pharmacology Male Middle Aged Proto-Oncogene Proteins c-bcl-2/metabolism Receptors, Interleukin-2/metabolism bcl-2-Associated X Protein/metabolism
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