on October 16, 2006
Published online before print October 16, 2006, doi: 10.1161/CIRCULATIONAHA.106.627430
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Submitted on March 16, 2006
From the Division of Cardiology, Department of Medicine, University Hospital, Foundation for Medical Researches, Geneva, Switzerland (S.S., F.B., G.P., F.M.); NovImmune SA, Geneva, Switzerland (Y.D., G.E., M.K.-V.); and INSERM U580, Hôpital Necker, Paris, France (L.C.). * To whom correspondence should be addressed. E-mail: Francois.Mach{at}medecine.unige.ch.
Background--Atherosclerosis is a chronic inflammatory disease of the large arteries that is the primary cause of heart disease and stroke. Anti-CD3-specific antibodies suppress immune responses by antigenic modulation of the CD3 antibody/T-cell receptor complex. Their unique capacity to restore self-tolerance in a mouse model of diabetes and, importantly, in patients with recent-onset type 1 diabetes involves transforming growth factor- Methods and Results--Low-density lipoprotein receptor-deficient mice were fed a high-cholesterol diet for 13 or 24 weeks. Anti-CD3 antibody was administered on 5 consecutive days beginning 1 week before or 13 weeks after the high-cholesterol diet was initiated, respectively. Control mice were injected in parallel with phosphate-buffered saline. Anti-CD3 antibody therapy reduced plaque development when administered before a high-cholesterol diet and markedly decreased lesion progression in mice with already established atherosclerosis. We found increased production of the antiinflammatory cytokine transforming growth factor- Conclusions--Altered disease progression, combined with the emergence of this particular cytokine pattern, indicates that short-term treatment with an anti-CD3 antibody induces a regulatory T-cell phenotype that restores self-tolerance in a mouse model of atherosclerosis.
Revised on July 7, 2006
Accepted on July 28, 2006
Short-Term Treatment With Anti-CD3 Antibody Reduces the Development and Progression of Atherosclerosis in Mice
Sabine Steffens PhD,
-dependent mechanisms via expansion and/or activation of regulatory T cells. We hypothesized that treatment with anti-CD3-specific antibodies might inhibit atherosclerosis development and progression in mice. in concanavalin A-stimulated lymph node cells and enhanced expression of the regulatory T-cell marker Foxp3 in spleens of anti-CD3 antibody-treated mice. A higher percentage of apoptotic cells within the plaques of anti-CD3 antibody-treated mice was also observed.
Key words: apoptosis • atherosclerosis • Foxp3 protein, mouse • immunology • inflammation • T-lymphocytes, regulatory • transforming growth factor beta
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