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on December 15, 2005

Arteriosclerosis, Thrombosis, and Vascular Biology. 2005
Published online before print December 15, 2005, doi: 10.1161/01.ATV.0000200380.73876.d9
A more recent version of this article appeared on March 1, 2006
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Submitted on May 5, 2005
Accepted on December 5, 2005

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 ; Pierre Boutouyrie ; Srini V. Kaveri ; Antonino Nicoletti ; and Antoine Lafont

From INSERM EMI 0016 (G.C., D.U., A.L.), Université René Descartes, Paris; Inserm U681 (G.C., E.G., N.M., S.V.K., A.N.), Université Pierre et Marie Curie (UPMC), Paris; Georges Pompidou European Hospital (P.R., P.J., D.M., A.L.), INSERM U698 (V.O.), and INSERM U652 (P.B.), Paris, France.

* To whom correspondence should be addressed. 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.
Key words: aortic diseases • immune system • blood cells




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