Transient role for CD1d-restricted natural killer T cells in the formation of atherosclerotic lesions

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. 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.