Skip Navigation


NDT Advance Access originally published online on September 7, 2004
Nephrology Dialysis Transplantation 2004 19(11):2713-2720; doi:10.1093/ndt/gfh423
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
19/11/2713    most recent
gfh423v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (18)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Schoop, R.
Right arrow Articles by Wüthrich, R. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schoop, R.
Right arrow Articles by Wüthrich, R. P.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nephrol Dial Transplant Vol. 19 No. 11 © ERA-EDTA 2004; all rights reserved

Original Article

Suppressed T-cell activation by IFN-{gamma}-induced expression of PD-L1 on renal tubular epithelial cells

Roland Schoop1, Patricia Wahl1, Michel Le Hir2, Uwe Heemann3, Minghui Wang3 and Rudolf P. Wüthrich1

1 Division of Nephrology, Kantonsspital St Gallen, Switzerland, 2 Institute of Anatomy, University of Zürich, Switzerland and 3 Department of Nephrology, TU-Klinikum rechts der Isar, Munich, Germany

Correspondence and offprint requests to: Prof. Dr R. P. Wüthrich, Renal Division, University Hospital, Rämistrasse 100, 8091 Zürich, Switzerland. Email: rudolf.wuethrich{at}usz.ch The authors wish it to be known that, in their opinion, the first two authors contributed equally to this work

Background. The interaction of the T-cell molecule PD-1 (programmed death-1) with its ligands PD-L1 and PD-L2 represents a known mechanism of T-cell inhibition. PD-1 is homologous to CD28 while the PD-1 ligands share homology with the B7 family of co-stimulatory molecules.

Methods. We have studied surface expression and transcript levels of PD-L1 and PD-L2 on murine renal tubular epithelial cells (TEC) by flow cytometric analysis and reverse transcription–polymerase chain reaction. Western blot analysis was used to confirm protein expression of PD-L1. We also tested the functional role of PD-L1 and PD-1 in antigen presentation. Furthermore, we stained mouse kidney transplants with rejection for the expression of the PD-1 ligands.

Results. We found that PD-L1 but not PD-L2 was weakly expressed on unstimulated TEC. Upon stimulation with IFN-{gamma}, a dose-dependent upregulation of PD-L1 expression was observed. Blockade of the PD-L1/PD-1 pathway with monoclonal antibodies in antigen presentation assays uncovered an inhibitory role of this ligand system in Th1 and Th2 cell activation. Staining for PD-L1 was strong in proximal and distal tubules in mouse kidney transplants with rejection, whereas staining of normal kidneys and syngenic mouse kidney transplants did not reveal PD-L1 expression. PD-L2 was not observed in normal or rejected mouse kidneys.

Conclusions. These data demonstrate that PD-L1 is an inducible renal tubular epithelial antigen that negatively regulates T-cell responses elicited by IFN-{gamma}-stimulated TEC. We speculate that the PD-1/PD-L1 pathway may play a role in protecting the epithelium from immune-mediated tubulointerstitial injury.

Keywords: antigen presentation; co-stimulation; PD-1; PD-L1; PD-L2; renal tubular epithelial cells


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Am. Soc. Nephrol.Home page
K. L. Edgtton, J. Y. Kausman, M. Li, K. O'Sullivan, C. Lo, P. Hutchinson, H. Yagita, S. R. Holdsworth, and A. R. Kitching
Intrarenal Antigens Activate CD4+ Cells via Co-stimulatory Signals from Dendritic Cells
J. Am. Soc. Nephrol., March 1, 2008; 19(3): 515 - 526.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
J. Yang, J. Popoola, S. Khandwala, N. Vadivel, V. Vanguri, X. Yuan, S. Dada, I. Guleria, C. Tian, M. J. Ansari, et al.
Critical Role of Donor Tissue Expression of Programmed Death Ligand-1 in Regulating Cardiac Allograft Rejection and Vasculopathy
Circulation, February 5, 2008; 117(5): 660 - 669.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
J. Menke, J. A. Lucas, G. C. Zeller, M. E. Keir, X. R. Huang, N. Tsuboi, T. N. Mayadas, H. Y. Lan, A. H. Sharpe, and V. R. Kelley
Programmed Death 1 Ligand (PD-L) 1 and PD-L2 Limit Autoimmune Kidney Disease: Distinct Roles
J. Immunol., December 1, 2007; 179(11): 7466 - 7477.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
Y. Waeckerle-Men, A. Starke, and R. P. Wuthrich
PD-L1 partially protects renal tubular epithelial cells from the attack of CD8+cytotoxic T cells
Nephrol. Dial. Transplant., June 1, 2007; 22(6): 1527 - 1536.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
M. E. Keir, S. C. Liang, I. Guleria, Y. E. Latchman, A. Qipo, L. A. Albacker, M. Koulmanda, G. J. Freeman, M. H. Sayegh, and A. H. Sharpe
Tissue expression of PD-L1 mediates peripheral T cell tolerance
J. Exp. Med., April 17, 2006; 203(4): 883 - 895.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.