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.
Major
Amy S
AS
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
Wilson
Michael T
MT
McCaleb
Jennifer L
JL
Ru Su
Yan
Y
Stanic
Aleksandar K
AK
Joyce
Sebastian
S
Van Kaer
Luc
L
Fazio
Sergio
S
Linton
Macrae F
MF
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