Immune-deficient mice develop typical atherosclerotic fatty streaks when fed an atherogenic diet

Abstract

Inbred strain C57BL/6J mice develop typical atherosclerotic fatty streaks in the aorta after 15 wk on a high fat, high cholesterol diet. To investigate the effects of the immune system on the development of fatty streaks in this model, C57BL/6J mice with a normal immune system were compared with C57BL/6J mice carrying mutations resulting in various immune deficiencies. These included mice with severe combined immune deficiency, athymic "nude" mice, class I MHC deficient mice, and class II MHC deficient mice. Despite similar lipoprotein profiles, lesion development in the immune compromised strains was similar to or increased compared with normal C57BL/6J mice. Class I MHC deficient mice demonstrated a threefold increase in lesion area (22,961 +/- 6,653 vs 8,868 +/- 1,817 microns2, P = 0.01). Immunohistochemical analysis of lesions showed characteristic features of atherosclerosis with vascular cell adhesion molecule-1 expression, immunoglobulin deposition, monocyte infiltration, and smooth muscle cell proliferation. These data indicate that the classical immune system, while not essential for atherosclerotic fatty streak development, may act to suppress the development of lesions.