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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/).

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This article has been cited by other articles:

• 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]  

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