Activation of T-lymphocytes by LDL-cholesterol

Native LDL-cholesterol can be mechanically stressed by strong vortexing. According to one hypothesis, mechanical shear stress within the vessel can lead to an aggregation of LDL-cholesterol and subsequently to activation of CD4 and CD8 T-lymphocytes. The goal of this study was to determine the proportion of activated CD4 and CD8 T-lymphocytes that is induced by adding unstressed and mechanically stressed LDL-cholesterol to whole blood samples. Whole blood was taken from 12 healthy subjects. All probands fasted for at least 12 h before blood withdrawal. In each case, 1 ml of whole blood from each subject was incubated for 16 h at 32 degrees C (89.3 degrees F) with concanavalin A (A), without additive (B), with mechanically stressed LDL-cholesterol (C) or with native LDL-cholesterol (D). Subsequently, the samples were measured by four-color flow cytometry. CD3, CD4, CD8, and CD69 were measured as activity markers. CD69 was plotted against CD4 and CD8, and the proportions of activated CD4 and CD8 T-lymphocytes were determined. Native and vortexed LDL-cholesterol elicited significantly different types of T-cell activation. While native LDL activated CD4 T-cells to only a small extent, mechanically stressed (vortexed) LDL potently activated CD8 T-cells. Purely mechanically-induced changes in LDL-cholesterol may be one mechanism that contributes to the activation of CD8 cells and, as a consequence, the emergence of arteriosclerosis.