Lymphocyte Populations in Atherosclerotic Lesions of ApoE −/− and LDL Receptor −/− Mice

Abstract

Lymphocytes are prominent components of human atherosclerotic lesions, but their presence in murine models of disease has not been confirmed. Lymphocyte subpopulations have been identified in apoE −/− and LDL receptor −/− mice fed a cholesterol-enriched diet for up to 3 months. ApoE −/− mice had higher serum cholesterol concentrations than did LDL receptor −/− mice during most of the feeding period, primarily due to large increases in VLDL concentrations. Total area of atherosclerotic lesions was greater at all times in apoE −/− than LDL receptor −/− mice (lesion area after 3 months on cholesterol-enriched diet: apoE −/−, 993±193 and LDL receptor −/−, 560±131 μm 2 ×10 3 , mean±SEM, n=6 in each group). Lesions in apoE −/− mice contained larger macrophage-rich necrotic cores and more calcification than did those in LDL receptor −/− mice. Immunocytochemical analyses of tissue sections of ascending aortas performed with monoclonal antibodies to T and B lymphocytes and macrophages revealed that T lymphocytes immunoreactive for Thy 1.2, CD5, CD4, and CD8 were observed in lesions from both strains, but no B lymphocytes were detected. The density of Thy 1.2 + T lymphocytes in lesions was greatest at 1 month (apoE −/−, 98±23 and LDL receptor −/−, 201±40 lymphocytes/mm 2 , n=6 in each group), decreasing in apoE −/− mice to 12±3 and in LDL receptor −/− mice to 51±20 lymphocytes/mm 2 at 3 months. The presence of T lymphocytes in murine atherosclerotic lesions makes these animals potentially useful for studying the involvement of the immune system in atherogenesis.