The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 QUICK SEARCH:   [advanced]


     
 


The Journal of Immunology, 2007, 179, 6536 -6546
Copyright © 2007 by The American Association of Immunologists, Inc.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Rao, D. A.
Right arrow Articles by Pober, J. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rao, D. A.
Right arrow Articles by Pober, J. S.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH

IL-1{alpha} and IL-1β Are Endogenous Mediators Linking Cell Injury to the Adaptive Alloimmune Response1

Deepak A. Rao*, Kevin J. Tracey§ and Jordan S. Pober2,*,{dagger},{ddagger}

* Department of Immunobiology, {dagger} Department of Pathology, and {ddagger} Department of Dermatology, Yale University School of Medicine, New Haven, CT 06510; and § Laboratories of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset, NY 11030

Preoperative or perioperative ischemic injury of allografts predisposes to graft arteriosclerosis, the major cause of late graft failure. We hypothesize that injured tissues release mediators that increase the production of pathogenic cytokines by alloreactive T cells. We find that freeze-thaw lysates of human endothelial cells (EC) increase both IFN-{gamma} and IL-17 production by human CD4+ T cells activated by HLA-DR+ allogeneic EC. Immunoadsorption of high-mobility group box 1 protein (HMGB1) reduces this activity in the lysates by about one-third, and recombinant HMGB1 increases T cell cytokine production. HMGB1 acts by inducing IL-1β secretion from contaminating monocytes via TLR4 and CD14. Upon removal of contaminating monocytes, the remaining stimulatory activity of EC lysates is largely attributable to IL-1{alpha}. Recombinant IL-1 directly augments IFN-{gamma} and IL-17 production by activated memory CD4+ T cells, which express IL-1R1. Furthermore, IL-1 increases the frequency of alloreactive memory CD4+ T cells that produce IL-17, but not those that produce IFN-{gamma}, in secondary cultures. Our results suggest that IL-1, released by injured EC or by HMGB1-stimulated monocytes, is a key link between injury and enhanced alloimmunity, offering a new therapeutic target for preventing late graft failure.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by grants from the National Institutes of Health National Heart, Lung, and Blood Institute (to J.S.P.) and National Institute of General Medical Sciences to (K.J.T.). D.A.R. is supported by the Medical Scientist Training Program.

2 Address correspondence and reprint requests to Dr. Jordan S. Pober, Yale University School of Medicine, Amistad Building, 10 Amistad Street, New Haven, CT 06509. E-mail address: jordan.pober{at}yale.edu

3 Abbreviations used in this paper: EC, endothelial cell; AGER, advanced glycosylation end product-specific receptor; HMGB1, high-mobility group box 1; ICS, intracellular cytokine staining.




This article has been cited by other articles:


Home page
Proc. Natl. Acad. Sci. USAHome page
C. Cayrol and J.-P. Girard
The IL-1-like cytokine IL-33 is inactivated after maturation by caspase-1
PNAS, June 2, 2009; 106(22): 9021 - 9026.
[Abstract] [Full Text] [PDF]


Home page
Proc. Natl. Acad. Sci. USAHome page
S. Z. Ben-Sasson, J. Hu-Li, J. Quiel, S. Cauchetaux, M. Ratner, I. Shapira, C. A. Dinarello, and W. E. Paul
IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation
PNAS, April 28, 2009; 106(17): 7119 - 7124.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
P. C.Y. Tang, L. Qin, J. Zielonka, J. Zhou, C. Matte-Martone, S. Bergaya, N. van Rooijen, W. D. Shlomchik, W. Min, W. C. Sessa, et al.
MyD88-dependent, superoxide-initiated inflammation is necessary for flow-mediated inward remodeling of conduit arteries
J. Exp. Med., December 22, 2008; 205(13): 3159 - 3171.
[Abstract] [Full Text] [PDF]


Home page
JEMHome page
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]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2007 by The American Association of Immunologists, Inc. All rights reserved.