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(American Journal of Pathology. 2007;170:1100-1107.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.060188

Characterization of the Natural Killer T-Cell Response in an Adoptive Transfer Model of Atherosclerosis

Paul A. VanderLaan, Catherine A. Reardon, Yuval Sagiv, Lydia Blachowicz, John Lukens, Michael Nissenbaum, Chyung-Ru Wang and Godfrey S. Getz

From the Department of Pathology, The University of Chicago, Chicago, Illinois

Natural killer T (NKT) cells have recently been implicated in atherogenesis, primarily for their ability to recognize and respond to lipid antigens. Because the atherosclerotic lesion is characterized by the retention and modification of lipids in the vascular wall, NKT cells may be involved in promoting the local vascular inflammatory response. Here, we investigate the proatherogenic role of NKT cells in an adoptive transfer model of atherosclerosis, using as recipients immune-deficient, atherosclerosis-susceptible RAG1–/–LDLR–/– mice. The adoptive transfer of an NKT cell-enriched splenocyte population from V{alpha}14J{alpha}18 T-cell receptor transgenic mice resulted in a 73% increase in aortic root lesion area compared with recipients of NKT cell-deficient splenocytes derived from CD1d–/– mice after 12 weeks of Western-type diet feeding. The total serum from hypercholesterolemic mice leads to a small but significant activation of V{alpha}14J{alpha}18 T-cell receptor-expressing hybridoma line by dendritic cells that is CD1d-dependent. Therefore, these studies demonstrate that NKT cells are proatherogenic in the absence of exogenous stimulation, and this activity is likely associated with endogenous lipid antigens carried by lipoproteins in the circulation and perhaps also in the atherosclerotic plaque.




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