2015 Russell Ross Memorial Lecture in Vascular Biology: Protective Autoimmunity in Atherosclerosis

Arterioscler Thromb Vasc Biol. 2016 Mar;36(3):429-38. doi: 10.1161/ATVBAHA.115.306009. Epub 2016 Jan 28.

Abstract

Atherosclerosis is an inflammatory disease of the arterial wall. It is accompanied by an autoimmune response against apolipoprotein B-100, the core protein of low-density lipoprotein, which manifests as CD4 T cell and antibody responses. To assess the role of the autoimmune response in atherosclerosis, the nature of the CD4 T cell response against apolipoprotein B-100 was studied with and without vaccination with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides. The immunologic basis of autoimmunity in atherosclerosis is discussed in the framework of theories of adaptive immunity. Older vaccination approaches are also discussed. Vaccinating Apoe(-/-) mice with major histocompatibility complex-II-restricted apolipoprotein B-100 peptides reduces atheroma burden in the aorta by ≈40%. The protective mechanism likely includes secretion of interleukin-10. Protective autoimmunity limits atherosclerosis in mice and suggests potential for developing preventative and therapeutic vaccines for humans.

Keywords: apolipoprotein B; atherosclerosis; immune system; immunology; lymphocyte.

Publication types

  • Lecture
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Animals
  • Apolipoprotein B-100 / administration & dosage
  • Apolipoprotein B-100 / immunology*
  • Apolipoprotein B-100 / metabolism
  • Apolipoproteins E / deficiency
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / immunology
  • Atherosclerosis / metabolism
  • Atherosclerosis / prevention & control*
  • Autoantibodies / immunology
  • Autoantibodies / metabolism
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Autoimmunity*
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Disease Models, Animal
  • Humans
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Mice, Transgenic
  • Protective Factors
  • Risk Factors
  • Vaccines, Subunit / administration & dosage

Substances

  • Apolipoprotein B-100
  • Apolipoproteins E
  • Autoantibodies
  • Autoantigens
  • Vaccines, Subunit