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(Circulation Research. 2005;96:675.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Atherosclerotic Abdominal Aortic Aneurysm and the Interaction Between Autologous Human Plaque-Derived Vascular Smooth Muscle Cells, Type 1 NKT, and Helper T Cells

Woon Ling Chan, Nada Pejnovic, Hamish Hamilton, Tze Vun Liew, Dusan Popadic, Alessandro Poggi, Shazia M. Khan

From the Department of Biochemical Pharmacology (W.L.C., N.P., T.V.L., D.P.), William Harvey Research Institute, Queen Mary, University of London, London, UK; General Surgery (H.H., S.M.K.), Barnet and Chase Farm Hospital, Enfield, UK; and the Laboratory of Immunology (A.P.), National Institute for Cancer Research, Genoa, Italy.

Correspondence to Dr Woon Ling Chan, Department of Biochemical Pharmacology, William Harvey Research Institute, Queen Mary, University of London, London EC1M 6BQ, UK. E-mail w.l.chan{at}qmul.ac.uk

Immune cell infiltration, vascular smooth muscle cell (VSMC) proliferation, and apoptosis are pathological hallmarks of atherosclerosis. The multifocal, chronic, and inflammatory nature of this disease of the cardiovascular system complicates targeted cellular therapy and emphasizes the need to understand the role and interaction of immune cells with VSMCs. We characterized the immune cell subsets present in human atherosclerotic tissue derived from atherosclerotic abdominal aortic aneurysm (AAA) and expanded them to study their interaction with autologous plaque-derived VSMCs in vitro. We show here that apart from T lymphocytes, plaque infiltrates consist of lots of NK cells and significant proportions of NKT cells that express T cell receptor (TCR) ß, CD4, and the NK markers CD56 and CD161. The infiltrates are predominantly IFN-–producing Type 1 lymphoid cells. When cocultured, the T and NKT cells adhere to VSMCs. CD4⁺ T cells enhance VSMC proliferation. VSMCs in turn enhance CD4⁺CD161⁺ NKT but not CD4⁺ or CD8⁺ T cell proliferation. CD4⁺CD161⁺ NKT cells inhibit VSMC proliferation by inducing apoptosis. Our results suggest that the interactions of Type 1 CD4⁺ T and CD4⁺CD161⁺ NKT cells with VSMCs may regulate VSMC proliferation and death respectively in atherosclerosis and the balance of these interactions could determine plaque stability.

Key Words: atherosclerotic abdominal aortic aneurysm • helper T cells • NKT • vascular smooth muscle cells • atherosclerosis

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