The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 June 2004. doi:10.1084/jem.20040139
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 11, 1455-1465
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 268K)
Right arrow PPT slides of all figures
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 Tang, Q.
Right arrow Articles by Bluestone, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tang, Q.
Right arrow Articles by Bluestone, J. A.
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?
In Vitro–expanded Antigen-specific Regulatory T Cells Suppress Autoimmune Diabetes

Qizhi Tang1, Kammi J. Henriksen1, Mingying Bi1, Erik B. Finger1, Greg Szot1, Jianqin Ye1, Emma L. Masteller1, Hugh McDevitt2, Mark Bonyhadi3, and Jeffrey A. Bluestone1

1 UCSF Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, CA 94143
2 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305
3 Xcyte Therapies, Inc., Seattle, WA 98104

Address correspondence to Jeffrey A. Bluestone, UCSF Diabetes Center, University of California San Francisco, Box 0540, 513 Parnassus Avenue, San Francisco, CA 94143. Phone: (415) 514-1683; Fax: (415) 564-5813; email: jbluest{at}diabetes.ucsf.edu

The low number of CD4+ CD25+ regulatory T cells (Tregs), their anergic phenotype, and diverse antigen specificity present major challenges to harnessing this potent tolerogenic population to treat autoimmunity and transplant rejection. In this study, we describe a robust method to expand antigen-specific Tregs from autoimmune-prone nonobese diabetic mice. Purified CD4+ CD25+ Tregs were expanded up to 200-fold in less than 2 wk in vitro using a combination of anti-CD3, anti-CD28, and interleukin 2. The expanded Tregs express a classical cell surface phenotype and function both in vitro and in vivo to suppress effector T cell functions. Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity.

Key Words: autoimmunity • tolerance • CD4+CD25+ T cells • NOD mice • immunoregulation

Abbreviations used in this paper: APC, allophycocyanin; CFSE, carboxyfluorescein diacetate succinimidyl ester; Ct, threshold cycle(s); GITR, glucocorticoid-induced TNF receptor; GAD, glutamic acid decarboxylase; NOD, nonobese diabetic; T1D, type 1 diabetes; Teff, T effector cell; Tg, transgenic; Treg, regulatory T cell.


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