In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
Abstract:
Atherosclerosis, an inflammatory disease of large arteries, is - through its clinical manifestations stroke and myocardial infarction - the leading cause of morbidity and mortality in the industrialized world. Adaptive immunity and co-stimulatory signals play a pivotal role during all stages of the disease. Recently, regulatory T cells (Treg) were attributed an anti-inflammatory and anti-atherogenic role. The interaction of CD70, a member of the tumor necrosis factor super family with its receptor CD27 modulates Treg development but also affects T cell proliferation, differentiation, and activation at the sites of antigen priming and at effector function. We hypothesized an increased atherosclerotic burden and an exacerbation of disease upon CD27 deficiency. Cd27+/+Apoe-/- or Cd27-/-Apoe-/- bone marrow was transplanted into Apoe-/- recipient mice. After reconstitution, mice were fed a 0.15% high fat/cholesterol diet for 6 weeks. Plaque area at the aortic sinus was increased 2.3-fold in Cd27-/-Apoe-/- chimeras. Plaques contained high amounts of macrophages, which was accompanied by a reduced frequency of aortic (54.1%) and splenic (17.7%) Tregs. Similar results were obtained in 18 wk old Cd27-/-Apoe-/- on a normal chow diet, that also displayed an increase in atherosclerotic plaque area and a 2.5-fold higher plaque macrophage content. In addition, Cd27-/-Apoe-/-mice showed a significant decrease in the abundance of splenic (26%) and aortic (27%) Tregs. Remarkably, 28 week-old Cd27-/-Apoe-/- mice did not exhibit this phenotype, suggesting that CD27 only plays a role in earlier stages of atherosclerosis. Although Cd27-/-Apoe-/- Tregs did not show changes in suppressive or migratory capacity compared to Cd27+/+Apoe-/-, Cd27-deficiency did result in a marked increase in thymic Treg apoptosis. Taken together, our data reveal that deficiency for CD27 impairs thymic Treg development, which thereby exacerbates early and intermediate atherosclerosis by increasing plaque inflammation.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.35.suppl_1.171
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1494427-3
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