Abstract 3694: Adoptive Transfer Of Immature Dendritic Cells Prevents Progression Of Established Atherosclerosis In LDLr−/− Mice
Introduction: We have previously shown that injection of oxLDL-pulsed mature dendritic cells (DCs), prior to the induction of atherosclerosis, strongly reduces atherosclerotic plaques. Treatment with immature DCs (imDCs) ameliorates autoimmune diseases by the induction of IL-10 producing regulatory T cells, resulting in peripheral tolerance. Therefore, the use of imDCs is an interesting approach and we investigated whether the transfer of imDCs may also be used as an immunotherapy to modulate established atherosclerosis.
Materials and Methods: Male LDLr−/− mice were fed a Western-type diet for 20 weeks. After 20 weeks of diet, the baseline level of atherosclerosis was determined in the aortic valves, the entire aorta, aortic arch and brachiocephalic artery. The other mice received 3 injections i.v. with either PBS or imDCs cultured from bone marrow (n=10; 1.5x106 cells per injection) and were put on the diet for another 10 weeks after which mice were sacrificed and lesion size was determined.
Results: The additional 10 week period of feeding of Western-type diet resulted in a 1.9 fold increase in plaques size in the aortic root in mice receiving PBS (7.59x105 μm2±3.88x104) as compared to the baseline group (4.06x105 μm2 ±7.22x104; P<0.001). The mice that received imDCs showed no significant increase in plaque size (4.74x105 μm2±4.45x104) compared to the baseline group. Analysis of the plaque area in the entire aorta showed that also at this site, plaque formation was not increased in the mice treated with imDCs compared to the baseline group (baseline: 28.3%±4.5; PBS: 50.6%±2.5; imDCs: 35.9%±3.6). The same effect was also observed in the brachiocephalic artery and the aortic arch. Treatment of imDCs also induced a more stable plaque phenotype in the aortic arch. In addition, at sacrifice cholesterol levels were 41% lower in mice treated with imDCs. Furthermore, 3 days after treatment the injection of imDCs induced lymphoid cells with a regulatory phenotype that produce high levels of IL-10.
Conclusion: Our data show that the adoptive transfer of bone marrow derived imDCs to mice with established lesions prevents the progression of atherosclerosis by an effect of dendritic cells on anti-inflammatory cells and a lowering of blood cholesterol levels.