OXIDIZED LDL INDUCES ENHANCED ANTIBODY-FORMATION AND MHC CLASS II-DEPENDENT IFN-GAMMA PRODUCTION IN LYMPHOCYTES FROM HEALTHY-INDIVIDUALS

The early stages of atherosclerosis are characterized by penetration i nto the arterial intima by both T lymphocytes and monocytes. Some of t hese 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 proinfla mmatory effects, including enhanced adhesiveness of endothelial cells and monocytes, chemotaxis of monocytes and T cells, and T-cell activat ion. 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-cel l cytokine secretion pattern after exposure to oxLDL in vitro. In peri pheral blood mononuclear cells from healthy donors (n=27), a significa ntly enhanced number of INF-gamma-producing cells was detected by ELIS POT (P<.001) after stimulation with 5 mu g/mL oxLDL. In contrast, prod uction of interleukin-4, was not significantly enhanced after stimulat ion with oxLDL. OxLDL-induced IFN-gamma secretion and T-cell prolifera tion were completely inhibited by major histocomparibility complex (MH C) class II antibodies. Furthermore, oxLDL was found to enhance the an tibody secretion, indicating B-cell activation. Our results indicate t hat 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 induce s a cell-dependent immune reaction, which may play an important role i n the development of atherosclerosis.