This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tellides, G. Articles by Pober, J. S. Search for Related Content PubMed PubMed Citation Articles by Tellides, G. Articles by Pober, J. S. Related Collections Growth factors/cytokines Transplantation

(Circulation Research. 2007;100:622.)
© 2007 American Heart Association, Inc.

Reviews

Interferon- Axis in Graft Arteriosclerosis

George Tellides, Jordan S. Pober

From the Interdepartmental Program in Vascular Biology and Transplantation (G.T., J.S.P.) and the Departments of Surgery (G.T.) and Immunobiology (J.S.P.), Yale University School of Medicine, New Haven, Conn.

Correspondence to George Tellides, MD, PhD, 295 Congress Ave, BCMM 454, New Haven, CT 06510. E-mail george.tellides{at}yale.edu

This Review is part of a thematic series on Transplant Vasculopathy, which includes the following articles:

Interferon- Axis in Graft Arteriosclerosis

Antibody and Complement in Transplant Vasculopathy

Allograft Vasculopathy Versus Atherosclerosis

Vascular Remodeling in Transplant Vasculopathy

Chemokines and Transplant Vasculopathy

Stem Cells and Transplant Vasculopathy
William Baldwin and Jordan Pober Guest Editors

Cardiac transplantation is the most effective treatment for advanced heart failure. Despite improvements in immunosuppression therapy that prevent acute rejection, cardiac allografts fail at rates of 3% to 5% per posttransplant year. The hallmark morphological lesion of chronically failing cardiac allografts, also seen in chronic renal and liver graft failure, is luminal stenosis of blood vessels, especially of conduit arteries. Late graft failure results from widespread secondary ischemic injury to the graft parenchyma rather than direct immune-mediated damage. Although this process affects the entire graft vasculature, graft arteriosclerosis is a suitable term to describe the problem because it applies to different types of failing organs and because it emphasizes the central feature, namely an accelerated form of arterial injury and remodeling. The precise pathogenesis of graft arteriosclerosis is unknown. In this review, we make the case that the signature T-helper type 1 cytokine, interferon (IFN)-, is a key effector in graft arteriosclerosis, which, together with the IFN-–inducing cytokine interleukin-12 and IFN-–inducible chemokines such as CXCR3 ligands, constitute a positive feedback loop for T-cell activation, differentiation, and recruitment that we refer to as the IFN- axis. We evaluate the evidence to support this hypothesis in clinical observational and experimental animal studies. Additionally, we examine the regulation of IFN- production within the artery wall, the effects of IFN- on vessel wall cells, and the outcome of therapeutic agents on IFN- production and signaling. These observations lead us to suggest that new therapies for graft arteriosclerosis should be optimized which focus on reducing IFN- synthesis or actions.

Key Words: interferon- • coronary arteries • cardiac transplantation • T cells • vascular cells

This article has been cited by other articles:

				Z. Mikhak, A. Farsidjani, and A. D. Luster Endotoxin Augmented Antigen-Induced Th1 Cell Trafficking Amplifies Airway Neutrophilic Inflammation J. Immunol., June 15, 2009; 182(12): 7946 - 7956. [Abstract] [Full Text] [PDF]

				R. E. Eid, D. A. Rao, J. Zhou, S.-f. L. Lo, H. Ranjbaran, A. Gallo, S. I. Sokol, S. Pfau, J. S. Pober, and G. Tellides Interleukin-17 and Interferon-{gamma} Are Produced Concomitantly by Human Coronary Artery-Infiltrating T Cells and Act Synergistically on Vascular Smooth Muscle Cells Circulation, March 17, 2009; 119(10): 1424 - 1432. [Abstract] [Full Text] [PDF]

				D. A. Rao, R. E. Eid, L. Qin, T. Yi, N. C. Kirkiles-Smith, G. Tellides, and J. S. Pober Interleukin (IL)-1 promotes allogeneic T cell intimal infiltration and IL-17 production in a model of human artery rejection J. Exp. Med., December 22, 2008; 205(13): 3145 - 3158. [Abstract] [Full Text] [PDF]

				T. Quillard, S. Coupel, F. Coulon, J. Fitau, M. Chatelais, M.C. Cuturi, E. Chiffoleau, and B. Charreau Impaired Notch4 Activity Elicits Endothelial Cell Activation and Apoptosis: Implication for Transplant Arteriosclerosis Arterioscler Thromb Vasc Biol, December 1, 2008; 28(12): 2258 - 2265. [Abstract] [Full Text] [PDF]

				Y. Bai, U. Ahmad, Y. Wang, J. H. Li, J. C. Choy, R. W. Kim, N. Kirkiles-Smith, S. E. Maher, J. G. Karras, C. F. Bennett, et al. Interferon-{gamma} Induces X-linked Inhibitor of Apoptosis-associated Factor-1 and Noxa Expression and Potentiates Human Vascular Smooth Muscle Cell Apoptosis by STAT3 Activation J. Biol. Chem., March 14, 2008; 283(11): 6832 - 6842. [Abstract] [Full Text] [PDF]

				M. C. Cuffy, A. M. Silverio, L. Qin, Y. Wang, R. Eid, G. Brandacher, F. G. Lakkis, D. Fuchs, J. S. Pober, and G. Tellides Induction of Indoleamine 2,3-Dioxygenase in Vascular Smooth Muscle Cells by Interferon-{gamma} Contributes to Medial Immunoprivilege J. Immunol., October 15, 2007; 179(8): 5246 - 5254. [Abstract] [Full Text] [PDF]

				Y. Wang, Y. Bai, L. Qin, P. Zhang, T. Yi, S. A. Teesdale, L. Zhao, J. S. Pober, and G. Tellides Interferon-{gamma} Induces Human Vascular Smooth Muscle Cell Proliferation and Intimal Expansion by Phosphatidylinositol 3-Kinase Dependent Mammalian Target of Rapamycin Raptor Complex 1 Activation Circ. Res., September 14, 2007; 101(6): 560 - 569. [Abstract] [Full Text] [PDF]