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Updated: Jul 8, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Deficiency of invariant V alpha 14 natural killer T cells decreases atherosclerosis in LDL receptor null mice
Leah Rogers1, Sarah Burchat, Jessica Gage
1Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada.
Aims:
CD1d-restricted natural killer T (NKT) cells function by regulating numerous immune responses during innate and adaptive immunity. Depletion of all populations of CD1d-dependent NKT cells has been shown by several groups to reduce atherosclerosis in two different mouse models of the disease. In this study, we determined if removal of a single (V alpha 14) NKT cell population protects mice from the disease.
Methods And Results:
Targeted deletion of the J alpha 18 gene results in selective depletion of CD1d-dependent V alpha 14 NKT cells in C57BL/6 mice without affecting the population of other NKT, NK, and conventional T cells. Therefore, to study the effect of V alpha 14 NKT cell depletion on the progression of atherosclerosis, we examined the extent of lesion formation using paired littermate LDL receptor null mice that were either +/+ or -/- for the J alpha 18 gene following the feeding of these mice a cholesterol- and fat-enriched diet for 8 weeks. At the end of the study, we found no difference in either serum total- or lipoprotein-cholesterol distributions between groups. However, quantification of atherosclerosis revealed that V alpha 14 NKT cell deficiency significantly decreased lesion size in the aortic root (20-28%) and arch (28-38%) in both genders of mice. By coupling the techniques of laser capture microdissection with quantitative real-time RT-PCR, we found that expression of the proatherogenic cytokine interferon (IFN)-gamma was significantly reduced in lesions from J alpha 18-/- mice.
Conclusion:
This study is the first to identify a specific subpopulation of NKT cells that promotes atherosclerosis via a mechanism appearing to involve IFN-gamma expression.
Insights
Selective depletion of V alpha 14 natural killer T (NKT) cells significantly reduced atherosclerosis progression in mice. This specific NKT cell population appears to promote the disease by increasing interferon-gamma expression.
Area of Science:
- Immunology
- Cardiovascular Research
Background:
- Natural killer T (NKT) cells regulate immune responses.
- Previous studies showed depleting all NKT cells reduces atherosclerosis.
- The role of specific NKT cell subsets in atherosclerosis was unclear.
Purpose of the Study:
- To determine if removing the V alpha 14 NKT cell population protects against atherosclerosis.
- To investigate the specific contribution of V alpha 14 NKT cells to disease progression.
Main Methods:
- Used J alpha 18 gene deletion to selectively deplete V alpha 14 NKT cells in LDL receptor null mice.
- Fed mice a cholesterol- and fat-enriched diet for 8 weeks.
- Quantified atherosclerosis lesion size and analyzed cytokine expression in lesions.
Main Results:
- V alpha 14 NKT cell deficiency significantly reduced lesion size in the aortic root and arch.
- No significant differences in serum cholesterol levels were observed between groups.
- Reduced expression of the proatherogenic cytokine interferon-gamma (IFN-gamma) was found in lesions of deficient mice.
Conclusions:
- Identified V alpha 14 NKT cells as a specific subpopulation promoting atherosclerosis.
- The mechanism appears to involve the upregulation of IFN-gamma.
- This finding offers a potential target for atherosclerosis treatment.
