Quantitative and qualitative differences in proatherogenic NKT cells in apolipoprotein E-deficient mice

Amy S. Major, Michael T. Wilson, Jennifer L. McCaleb, Ru Su Yan, Aleksandar K. Stanic, Sebastian Joyce, Luc Van Kaer, Sergio Fazio, MacRae F. Linton

Research output: Contribution to journalArticlepeer-review

102 Scopus citations


Background - Atherosclerosis is a disease marked by lipid accumulation and inflammation. Recently, atherosclerosis has gained recognition as an autoimmune-type syndrome characterized by increased activation of the innate and acquired immune systems. Natural killer T (NKT) cells have characteristics of both conventional T cells and NK cells and recognize glycolipid antigens presented in association with CD1d molecules on antigen-presenting cells. The capacity of NKT cells to respond to lipid antigens and modulate innate and acquired immunity suggests that they may play a role in atherogenesis. Methods and Results - We examined the role of NKT cells in atherogenesis and how the atherosclerotic environment affects the NKT cell population itself. The data show that CD1d-deficiency in male apolipoprotein E-deficient (apoE0) mice results in reduction in atherosclerosis, and treatment of apoE0 mice with α-galactosylceramide, a potent and specific NKT cell activator, results in a 2-fold increase in atherosclerosis. Interestingly, we demonstrate that α-galactosylceramide-induced interferon-γ responses and numbers of NKT cells in apoE0 mice show age-dependent qualitative and quantitative differences as compared with age-matched wild-type mice. Conclusions - Collectively, these findings reveal that hyperlipidemia and atherosclerosis have significant effects on NKT cell responses and that these cells are proatherogenic.

Original languageEnglish (US)
Pages (from-to)2351-2357
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number12
StatePublished - Dec 2004
Externally publishedYes


  • Atherosclerosis
  • Autoimmunity
  • Cytokines
  • Inflammation
  • NKT lymphocytes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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