Journal
BLOOD
Volume 104, Issue 7, Pages 2051-2059Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-10-3485
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Funding
- NHLBI NIH HHS [HL68744] Funding Source: Medline
- NIAID NIH HHS [AI50953, AI42284] Funding Source: Medline
- NINDS NIH HHS [NS44044] Funding Source: Medline
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We have investigated the potential role of CD1d-restricted natural killer T (NKT) cells in the development of atherosclerosis in mice. When fed an atherogenic diet (AD), NKT cell-deficient CD1d(-/-) mice had significantly smaller atherosclerotic lesions than AD-fed C57BL/6 (wild-type [WT]) mice. A significant reduction in atherosclerotic lesions was also demonstrated in AD-fed, low-density lipoprotein receptor-deficient (Ldlr(-/-)) mice reconstituted with CD1d(-/-) bone marrow cells compared with the lesions observed in Ldlr(-/-) mice reconstituted with WT marrow cells. In addition, repeated injections of a-GalCer or the related glycolipid OCH to apolipoprotein E knockout (apoE(-/-)) mice during the early phase of atherosclerosis significantly enlarged the lesion areas compared with mice injected with vehicle control. However, administering alpha-GalCer to apoE(-/-) mice with established lesions did not significantly increase the lesion area but considerably decreased the collagen content. Atherosclerosis development in either AD-fed WT or apoE(-/-) mice was associated with the presence of Valpha14Jalpha18 transcripts in the atherosclerotic arterial walls, indicating that NKT cells were recruited to these lesions. Thioglycolate-elicited macrophages pulsed with oxidized low-density lipoproteins expressed enhanced CD1d levels and induced NKT cells to produce interferon-gamma, a potentially proatherogenic T-helper 1 (T(H)1) cytokine. Collectively, we conclude that NKT cells are proatherogenic in mice. (C) 2004 by The American Society of Hematology.
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