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

Major AS, Wilson MT, McCaleb JL, Ru Su Y, Stanic AK, Joyce S, Van Kaer L, Fazio S, Linton MF
Arterioscler Thromb Vasc Biol. 2004 24 (12): 2351-7

PMID: 15472130 · DOI:10.1161/01.ATV.0000147112.84168.87

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 (apoE(0)) mice results in reduction in atherosclerosis, and treatment of apoE(0) mice with alpha-galactosylceramide, a potent and specific NKT cell activator, results in a 2-fold increase in atherosclerosis. Interestingly, we demonstrate that alpha-galactosylceramide-induced interferon-gamma responses and numbers of NKT cells in apoE(0) 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.

MeSH Terms (16)

Age Factors Animals Antigens, CD1 Aorta Apolipoproteins E Arteriosclerosis Cytokines Galactosylceramides Killer Cells, Natural Lymphocyte Activation Lymphocyte Subsets Male Mice Mice, Inbred C57BL Phenotype Qualitative Research

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