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


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.
Department of Medicine, Division of Cardiovascular Medicine, 2220 Pierce Avenue, Room 383 PRB, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. amy.major@vanderbilt.edu
Amy S
AS
Major
Michael T
MT
Wilson
Jennifer L
JL
McCaleb
Yan
Y
Ru Su
Aleksandar K
AK
Stanic
Sebastian
S
Joyce
Luc
L
Van Kaer
Sergio
S
Fazio
Macrae F
MF
Linton
D000367:Age Factors; D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism / Q000502:physiology; D001011:Aorta / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency* / Q000502:physiology; D001161:Arteriosclerosis / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis; D005699:Galactosylceramides / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000502:physiology; D016131:Lymphocyte Subsets / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D036301:Qualitative Research
D018949:Antigens, CD1; D001057:Apolipoproteins E; D016207:Cytokines; D005699:Galactosylceramides; C493154:alpha-galactosylceramide