The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
A correction to this article has been published: J. Exp. Med. 198 (4) 677
Published 7 July 2003. doi:10.1084/jem.20022119
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 217K)
Right arrow PPT slides of all figures
Right arrow Correction (v198,p677)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Salama, A. D.
Right arrow Articles by Khoury, S. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Salama, A. D.
Right arrow Articles by Khoury, S. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© Rockefeller University Press, 0022-1007/2003/7/71 $5.00
The Journal of Experimental Medicine, Volume 198, Number 1, 71-78

Critical Role of the Programmed Death-1 (PD-1) Pathway in Regulation of Experimental Autoimmune Encephalomyelitis

Alan D. Salama1,3, Tanuja Chitnis2,3, Jaime Imitola2,3, Mohammed Javeed I. Ansari1, Hisaya Akiba4, Fumihiko Tushima5, Miyuki Azuma5, Hideo Yagita4, Mohamed H. Sayegh1,3 and Samia J. Khoury2

1 Laboratory of Immunogenetics and Transplantation, Brigham and Women's Hospital
2 Centre for Neurologic Diseases, Brigham and Women's Hospital
3 Division of Nephrology, Children's Hospital, Harvard Medical School, Boston, MA 02115
4 Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan
5 Department of Molecular Immunology, Tokyo Medical and Dental University, Tokyo 113-8549, Japan

Address correspondence to Samia J. Khoury, 77 Avenue Louis Pasteur, Room 714, Centre for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA 02115. Phone: 617-525-5370; Fax: 617-525-5252; E-mail: skhoury{at}rics.bwh.harvard.edu

Experimental autoimmune encephalomyelitis (EAE) is mediated by autoantigen-specific T cells dependent on critical costimulatory signals for their full activation and regulation. We report that the programmed death-1 (PD-1) costimulatory pathway plays a critical role in regulating peripheral tolerance in murine EAE and appears to be a major contributor to the resistance of disease induction in CD28-deficient mice. After immunization with myelin oligodendrocyte glycoprotein (MOG) there was a progressive increase in expression of PD-1 and its ligand PD-L1 but not PD-L2 within the central nervous system (CNS) of mice with EAE, peaking after 3 wk. In both wild-type (WT) and CD28-deficient mice, PD-1 blockade resulted in accelerated and more severe disease with increased CNS lymphocyte infiltration. Worsening of disease after PD-1 blockade was associated with a heightened autoimmune response to MOG, manifested by increased frequency of interferon {gamma}–producing T cells, increased delayed-type hypersensitivity responses, and higher serum levels of anti-MOG antibody. In vivo blockade of PD-1 resulted in increased antigen-specific T cell expansion, activation, and cytokine production. Interestingly, PD-L2 but not PD-L1 blockade in WT animals also resulted in disease augmentation. Our data are the first demonstration that the PD-1 pathway plays a critical role in regulating EAE.

Key Words: costimulation • T cell • autoimmunity • tolerance • EAE


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS