Mildly oxidized low-density lipoproteins suppress the proliferation of activated CD4+ T-lymphocytes and their interleukin 2 receptor expression in vitro

Activated T-lymphocytes are present in early atherosclerotic lesions where they may interact with oxidized low-density lipoproteins (oxLDLs). In this study the non-specific effect of oxLDLs on the activation of T-cells in vitro was investigated. LDLs were oxidized by UV irradiation and characterized by a low level of lipid peroxidation and only slight apolipoprotein B modification. Peripheral blood lymphocytes from normal individuals were stimulated in vitro with the polyclonal activator phytohaemagglutinin in the presence of various doses of LDLs and oxLDLs. LDLs enhanced the proliferation of peripheral blood lymphocytes at doses up to 100 mu g/ml but were inhibitory at 200 mu g/ml, whereas low doses of oxLDLs (over 10 mu g/ml) inhibited the proliferation. OxLDLs also inhibited the proliferative responses of an alloreactive CD4(+) T-cell line immortalized by Herpes virus saimiri and an influenza haemagglutinin-specific CD4(+) T-cell clone. Viability tests using Trypan Blue exclusion or expression of Apo2.7, an apoptosis marker, did not indicate any significant cell death at doses up to 100 mu g/ml oxLDL. At this concentration, cell-cycle analysis showed an accumulation of cells at the G(1)/S interface in the CD4(+) cell clone, without significant DNA fragmentation. The expression of the activation antigen CD25 on T-lymphocytes (on phytohaemagglutinin-activated T-cells and on CD4(+) T-cell clone), requisite to the commitment of activated T-cells from G, phase to S phase, was also inhibited by oxLDLs whereas expression of other activation antigens such as CD69 and HLA-DR was unchanged. In conclusion, these data show that mildly oxidized LDLs inhibit the proliferation and CD25 expression of activated T-lymphocytes and suggest that oxLDLs may slow down the T-cell response in atherosclerotic lesions.