Reduced Immunoregulatory CD31 + T Cells in Patients With Atherosclerotic Abdominal Aortic Aneurysm

Abstract

Background— Cell-mediated immunity is considered to contribute to the pathogenesis of abdominal aortic aneurysms (AAA). In particular, infiltrating macrophages and CD8 + T lymphocytes participate in the destruction of the aortic wall extracellular matrix and smooth muscle cells. We surmise that these pathological events are controlled by circulating regulatory lymphocytes. Methods and Results— Circulating CD4 + /CD31 + cells were reduced in AAA patients (n=80, 8.9±0.6%) as compared with controls (n=69, 13.7±0.8%; P <0.001) and inversely proportional to AAA size. Exclusion of the aneurysm by an endoprothesis did not affect CD31 + T cell values. Reduction of blood CD4 + /CD31 + cells was not attributable to their enrichment in AAA tissue. In contrast, CD8 + /CD31 + cells were slightly reduced in the blood while increased in the aneurysmal tissue (29.2±0.5 versus 20.2±4.7% in blood, n=6; P <0.05). Remarkably, high percentages of CD4 + /CD31 + cells were able to regulate proliferation and cytokine production of CD8 + lymphocytes, as well as CD8 + cell-mediated cytotoxicity of aortic smooth muscle cells ( P <0.01). Finally, CD4 + /CD31 + cells reduced the production and activity of metalloproteinase-9 by lipopolysaccharide-stimulated macrophages. Conclusions— Circulating CD4 + /CD31 + T cells regulate macrophage and CD8 + T cell activation and effector function in the arterial wall. Their reduction might promote the development of AAA.