This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 24/12/2351    most recent 01.ATV.0000147112.84168.87v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Major, A. S. Articles by Linton, M. F. Search for Related Content PubMed PubMed Citation Articles by Major, A. S. Articles by Linton, M. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Related Collections Animal models of human disease Pathophysiology Genetically altered mice Growth factors/cytokines

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:2351.)
© 2004 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Quantitative and Qualitative Differences in Proatherogenic NKT Cells in Apolipoprotein E–Deficient Mice

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

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.

Correspondence to Amy S. Major, Department of Medicine, Division of Cardiovascular Medicine, 2220 Pierce Avenue, Room 383 PRB, Vanderbilt University School of Medicine, Nashville, TN 37232 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 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.

Natural killer T (NKT) cells have characteristics of both T and NK cells and recognize glycolipid antigens. We show that NKT cell–deficiency in male apoE⁰ mice results in decreased atherosclerosis whereas activation of NKT cells resulted in a 2-fold increase in atherosclerosis. NKT cell numbers and functions are affected by the hyperlipidemia state.

Key Words: inflammation • atherosclerosis • NKT lymphocytes • cytokines • autoimmunity

This article has been cited by other articles:

				O. M. Kattan, F. B. Kasravi, E. L. Elford, M. T. Schell, and H. W. Harris Apolipoprotein E-Mediated Immune Regulation in Sepsis J. Immunol., July 15, 2008; 181(2): 1399 - 1408. [Abstract] [Full Text] [PDF]

				L. Rogers, S. Burchat, J. Gage, M. Hasu, M. Thabet, L. Wilcox, T. A. Ramsamy, and S. C. Whitman Deficiency of invariant V{alpha}14 natural killer T cells decreases atherosclerosis in LDL receptor null mice Cardiovasc Res, April 1, 2008; 78(1): 167 - 174. [Abstract] [Full Text] [PDF]

				P. A. VanderLaan, C. A. Reardon, Y. Sagiv, L. Blachowicz, J. Lukens, M. Nissenbaum, C.-R. Wang, and G. S. Getz Characterization of the Natural Killer T-Cell Response in an Adoptive Transfer Model of Atherosclerosis Am. J. Pathol., March 1, 2007; 170(3): 1100 - 1107. [Abstract] [Full Text] [PDF]

				A. K. Stanic, C. M. Stein, A. C. Morgan, S. Fazio, M. F. Linton, E. K. Wakeland, N. J. Olsen, and A. S. Major Immune dysregulation accelerates atherosclerosis and modulates plaque composition in systemic lupus erythematosus PNAS, May 2, 2006; 103(18): 7018 - 7023. [Abstract] [Full Text] [PDF]

				A. Tedgui and Z. Mallat Cytokines in Atherosclerosis: Pathogenic and Regulatory Pathways Physiol Rev, April 1, 2006; 86(2): 515 - 581. [Abstract] [Full Text] [PDF]

				R. Wessely Interference by interferons: Janus faces in vascular proliferative diseases Cardiovasc Res, June 1, 2005; 66(3): 433 - 443. [Abstract] [Full Text] [PDF]

				P. A. VanderLaan and C. A. Reardon Thematic review series: The Immune System and Atherogenesis. The unusual suspects:an overview of the minor leukocyte populations in atherosclerosis J. Lipid Res., May 1, 2005; 46(5): 829 - 838. [Abstract] [Full Text] [PDF]

				Y. V. Bobryshev, I. F. Charo, and A. M. Aslanian Natural Killer T Cells in Atherosclerosis Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): e40 - e40. [Full Text] [PDF]