Oxidized LDL Induces Enhanced Antibody Formation and MHC Class II–Dependent IFN-γ Production in Lymphocytes From Healthy Individuals

The early stages of atherosclerosis are characterized by penetration into the arterial intima by both T lymphocytes and monocytes. Some of these T lymphocytes show signs of activation, though the mechanisms by which they become activated are not known. The monocytes develop into macrophages and subsequently into foam cells filled with oxidized LDL (oxLDL)-derived lipids. OxLDL has been found to exert several proinflammatory effects, including enhanced adhesiveness of endothelial cells and monocytes, chemotaxis of monocytes and T cells, and T-cell activation. The enzyme-linked immunospot (ELISPOT) assay has been shown to be a sensitive method for detection of single cells secreting antibodies or cytokines. Here we have used this method to characterize the T-cell cytokine secretion pattern after exposure to oxLDL in vitro. In peripheral blood mononuclear cells from healthy donors (n = 27), a significantly enhanced number of INF-gamma-producing cells was detected by ELISPOT (P < .001) after stimulation with 5 micrograms/mL oxLDL. In contrast, production of interleukin-4 was not significantly enhanced after stimulation with oxLDL. OxLDL-induced IFN-gamma secretion and T-cell proliferation were completely inhibited by major histocompatibility complex (MHC) class II antibodies. Furthermore, oxLDL was found to enhance the antibody secretion, indicating B-cell activation. Our results indicate that oxLDL activates T cells by an MHC class II-dependent mechanism. In healthy individuals, oxLDL induces IFN-gamma, which is produced by T helper type 1-like cells. These findings demonstrate that oxLDL induces a cell-dependent immune reaction, which may play an important role in the development of atherosclerosis.