on October 7, 2004
Published online before print October 7, 2004, doi: 10.1161/01.ATV.0000147112.84168.87
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Submitted on June 7, 2004
Accepted on September 24, 2004
Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E-Deficient Mice
Amy S. Major *;
From the Departments of Medicine/Division of Cardiovascular Medicine (A.S.M., J.L.M., Y.R.S., S.F., M.F.L.), Microbiology and Immunology (M.T.W., A.K.S., S.J., L.V.K.), Pathology (S.F.), and Pharmacology (M.F.L.), Vanderbilt University School of Medicine, Nashville, Tenn.
* To whom correspondence should be addressed. E-mail: amy.major{at}vanderbilt.edu.
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 
-galactosylceramide, a potent and specific NKT cell activator, results in a 2-fold increase in atherosclerosis. Interestingly, we demonstrate that -galactosylceramide induced interferon-
responses in apoE0 mice and that 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.
Key words: inflammation • atherosclerosis • NKT lymphocytes • cytokines • autoimmunity
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