Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4595K) PDF+supp data (5444K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Rao, D. A. Articles by Pober, J. S. Search for Related Content PubMed PubMed Citation Articles by Rao, D. A. Articles by Pober, J. S. Social Bookmarking                            What's this?

¹ Department of Immunobiology, ² Department of Surgery, ³ Department of Pathology, and ⁴ Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510

CORRESPONDENCE Jordan S. Pober: jordan.pober{at}yale.edu

Interleukin (IL) 1 produced by human endothelial cells (ECs), in response to tumor necrosis factor (TNF) or to co-culture with allogeneic T cells in a TNF-dependent manner, can augment the release of cytokines from alloreactive memory T cells in vitro. In a human–mouse chimeric model of artery allograft rejection, ECs lining the transplanted human arteries express IL-1, and blocking IL-1 reduces the extent of human T cell infiltration into the artery intima and selectively inhibits IL-17 production by infiltrating T cells. In human skin grafts implanted on immunodeficient mice, administration of IL-17 is sufficient to induce mild inflammation. In cultured cells, IL-17 acts preferentially on vascular smooth muscle cells rather than ECs to enhance production of proinflammatory mediators, including IL-6, CXCL8, and CCL20. Neutralization of IL-17 does not reduce T cell infiltration into allogeneic human artery grafts, but markedly reduces IL-6, CXCL8, and CCL20 expression and selectively inhibits CCR6⁺ T cell accumulation in rejecting arteries. We conclude that graft-derived IL-1 can promote T cell intimal recruitment and IL-17 production during human artery allograft rejection, and suggest that targeting IL-1 in the perioperative transplant period may modulate host alloreactivity.

D.A. Rao and R.E. Eid contributed equally to this paper.

G. Tellides and J.S. Pober contributed equally to this paper.

© 2008 Rao et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Thebault, P., Lhermite, N., Tilly, G., Le Texier, L., Quillard, T., Heslan, M., Anegon, I., Soulillou, J.-P., Brouard, S., Charreau, B., Cuturi, M.-C., Chiffoleau, E. (2009). The C-Type Lectin-Like Receptor CLEC-1, Expressed by Myeloid Cells and Endothelial Cells, Is Up-Regulated by Immunoregulatory Mediators and Moderates T Cell Activation. J. Immunol. 183: 3099-3108 [Abstract] [Full Text]  
• Eid, R. E., Rao, D. A., Zhou, J., Lo, S.-f. L., Ranjbaran, H., Gallo, A., Sokol, S. I., Pfau, S., Pober, J. S., Tellides, G. (2009). Interleukin-17 and Interferon-{gamma} Are Produced Concomitantly by Human Coronary Artery-Infiltrating T Cells and Act Synergistically on Vascular Smooth Muscle Cells. Circulation 119: 1424-1432 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS