Evidence for a local immune response in atherosclerosis. CD4+ T cells infiltrate lesions of apolipoprotein-E-deficient mice

Am J Pathol. 1996 Aug;149(2):359-66.


It has been suggested that immune responses are involved in the development of atherosclerosis. We have evaluated this possibility by analyzing immunocompetent cells in a murine model of the disease. Apolipoprotein E knockout (apoE -/-) mice are genetically hypercholesterolemic due to targeted disruption of the apolipoprotein E gene and develop severe atherosclerosis. Such mice were fed either standard pellets or a diet containing 1.25% cholesterol. Lesions were analyzed from mice at 9 and 16 weeks of age. Immunohistochemical staining of fatty streaks showed that CD4+ T cells were frequent, both in clusters and as single cells. In advanced atherosclerotic plaques, CD4+ T cells were prominent in the fibrous cap and subendotbelially, whereas CD8+ T cells were sparse. The CD25 subunit of the interleukin-2 receptor, which is a marker for activated T cells, was expressed in CD4-rich areas and the major histocompatibility complex class II antigen, I-A(b), which is induced by cytokines released from activated T cells, was also found in the lesions. These data indicate that CD4+ T cells participate in the formation of atherosclerotic lesions in genetically hypercholesterolemic apoE -/- mice. They suggest that immune activation is part of the disease process, and we speculate that a direct link may exist between cholesterol accumulation and T cell activation, possibly by autoimmune responses to modified lipoproteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / analysis
  • Apolipoproteins E / deficiency*
  • Arteriosclerosis / immunology*
  • Arteriosclerosis / pathology
  • Biomarkers / analysis
  • CD4-Positive T-Lymphocytes / immunology*
  • Hypercholesterolemia / complications
  • Immunohistochemistry
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Interleukin-2 / analysis


  • Antibodies, Monoclonal
  • Apolipoproteins E
  • Biomarkers
  • Receptors, Interleukin-2