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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:618.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

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

Giuseppina Caligiuri; Patrick Rossignol; Pierre Julia; Emilie Groyer; Dikran Mouradian; Dominique Urbain; Namita Misra; Véronique Ollivier; Marc Sapoval; Pierre Boutouyrie; Srini V. Kaveri; Antonino Nicoletti; Antoine Lafont

Institut National de la Santé et de la Recherche Medicale (INSERM), EMI0016 (G.C., D.U., A.L.), U681 (G.C., E.G., N.M., S.V.K., A.N.), U765 (P.R.), U698 (V.O.), and U652 (P.B.); Faculté de Médecine René Descartes Paris 5 (G.C., P.R., P.J., D.U., A.L.); Universite Pierre et Marie Curie (UPMC) Paris 6 (E.G., N.M., S.V.K., A.N.); Service de Médicine Vasculaire et Hypertension artérielle (P.R., D.M.), Service de Chirurgie Cardio-vasculaire (P.J.), and Service de Cardiologie (M.S., A.L.), Hôpital Européan Georges-Pompidou, AP-MP, Paris, France.

Correspondence to Giuseppina Caligiuri, MD, PhD, INSERM U681-Institut des Cordeliers, 15, rue de l’Ecole de Médecine, 75006 Paris, France. E-mail giuseppina.caligiuri{at}umrs681.jussieu.fr

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.

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. 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.

Key Words: aortic diseases • immune system • blood cells

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