Reduced immunoregulatory CD31+ T cells in patients with atherosclerotic abdominal aortic aneurysm

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.