LDL immunization induces T-cell-dependent antibody formation and protection against atherosclerosis

Atherosclerosis is an inflammatory disease, and the involvement of immune m echanisms in disease progression is increasingly recognized. Immunization w ith oxidized low density lipoprotein (LDL decreases atherosclerosis in seve ral animal models. To explore humoral and cellular immune reactions involve d in this protection, we immunized apolipoprotein E knockout mice with eith er homologous plaque homogenates or homologous malondialdehyde (MDA)-LDL. I mmunization with both these antigen preparations reduced lesion development . The plaques contained immunogen(s) sharing epitopes on MDA-LDL, MDA-very low density lipoprotein, and oxidized cardiolipin. This shows that a T-cell -dependent antibody response was associated with protection against atheros clerosis. The protection was associated with specific T-cell-dependent elev ation of IgG antibodies against MDA-LDL and oxidized phospholipids, and the increased titers of IgG antibodies were correlated with decreased lesion f ormation and lower serum cholesterol levels.