Oxidized low density lipoproteins induce apoptosis in PHA-activated peripheral blood mononuclear cells and in the Jurkat T-cell line

Oxidized low density lipoproteins (oxLDLs) and activated T lymphocytes are present in early atherosclerotic plaques. It has been shown that oxLDLs are cytotoxic to cultured vascular cells but their possible toxic action on T lymphocytes has not been described. Peripheral blood lymphocytes from healt hy individuals were stimulated in vitro with the polyclonal activator phyto hemagglutinin and treated with various doses of native and mildly oxidized LDLs, Low doses of oxLDLs inhibited cell growth and DNA synthesis after 48 h culture and at 200 mu g apoB/ml we observed a loss of cell viability. Dea d cells did not exhibit significant increase of alteration of membrane inte grity (i.e., necrosis) but showed chromatin fragmentation evaluated by DNA staining with 4',6-diamidino-2-phenylindole and propidium iodide, This frag mentation increased with TBARS and hydroperoxide levels. The expression of early apoptosis marker Apo2.7 rose among the CD3(+) T-cell population, In a ddition, morphological analysis showed apoptotic features (cell shrinking, nucleus condensation, and fragmentation), Study of phosphatidylserine expre ssion using Annexin V confirmed that oxLDLs induced apoptosis in activated lymphocytes. In the Jurkat T-cell line cultured with oxLDLs, apoptotic morp hological changes (condensation and nucleus fragmentation) were observed an d they were accompanied by DNA fragmentation visualized by propidium iodide staining and electrophoresis showing apoptotic ladder. These results demon strate that mildly oxidized LDLs induce apoptosis in a part of activated an d proliferating T cells. T-lymphocyte apoptosis induction in atheroscleroti c lesions might contribute to the development of an unappropriate local T c ell response.