TY - JOUR
T1 - Characterization of the natural killer T-cell response in an adoptive transfer model of atherosclerosis
AU - VanderLaan, Paul A.
AU - Reardon, Catherine A.
AU - Sagiv, Yuval
AU - Blachowicz, Lydia
AU - Lukens, John
AU - Nissenbaum, Michael
AU - Wang, Chyung Ru
AU - Getz, Godfrey S.
N1 - Funding Information:
Supported by the National Institutes of Health (grants HL056827 and HL068661 to G.S.G., and cardiovascular pathophysiology and biochemistry training grant HL007237 and medical scientist training program grant GM007281 to P.V.) and the Cancer Research Institute (to Y.S.).
PY - 2007/3
Y1 - 2007/3
N2 - 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 Vα14Jα18 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 Vα14Jα18 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.
AB - 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 Vα14Jα18 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 Vα14Jα18 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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U2 - 10.2353/ajpath.2007.060188
DO - 10.2353/ajpath.2007.060188
M3 - Article
C2 - 17322392
AN - SCOPUS:34247855183
VL - 170
SP - 1100
EP - 1107
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 3
ER -