on December 9, 2004
Published online before print December 9, 2004, doi: 10.1161/01.ATV.0000153046.59370.13
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Submitted on July 7, 2004
Accepted on November 3, 2004
Transient Role for CD1d-Restricted Natural Killer T Cells in the Formation of Atherosclerotic Lesions
Ara M. Aslanian ;
From the Gladstone Institute of Cardiovascular Disease (A.M.A., I.F.C.) and the Department of Medicine and Cardiovascular Research Institute (H.A.C., I.F.C.), University of California, San Francisco.
* To whom correspondence should be addressed. E-mail: icharo{at}gladstone.ucsf.edu.
Objective--CD1d-restricted natural killer T (NKT) cells are reported to play a proatherogenic role in the development of atherosclerosis. However, the contribution of NKT cells to mature lesion formation and the effector mechanisms through which they act are unknown.
Methods and Results--We measured lesion size in CD1d-null (CD1d-/-) mice on the low-density lipoprotein (LDL) receptor-deficient (LDLR-/-) genetic background after 4, 8, and 12 weeks of feeding on a Western diet. Lesions in CD1d-/-LDLR-/- mice were 47% smaller at 4 weeks than CD1d+/+LDLR-/- controls; however, there were no differences in lesion size between CD1d-/-LDLR-/- and CD1d+/+LDLR-/- mice at 8 or 12 weeks. Using real-time polymerase chain reaction, we found that although NKT cells were present in the aortic arch of CD1d+/+LDLR-/- mice on the Western diet, no differences in mRNA abundance for Th1 or Th2 cytokines were observed between CD1d-/-LDLR-/- and CD1d+/+LDLR-/- mice.
Conclusions--CD1d-restricted NKT cells contribute to the formation of fatty streaks; however, their influence on lesion progression is transient, and they do not significantly affect the inflammatory cytokine milieu of mature lesions.
Key words: atherosclerosis • cardiovascular diseases • inflammation • lipoproteins • lymphocytes
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