The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 7 March 2005. doi:10.1084/jem.20040685
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 5, 737-746
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1195K)
Right arrow PPT slides of all figures
Right arrow Supplemental Material Index
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 Fahlén, L.
Right arrow Articles by Powrie, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fahlén, L.
Right arrow Articles by Powrie, F.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 T cells that cannot respond to TGF-ß escape control by CD4+CD25+ regulatory T cells

Linda Fahlén1, Simon Read1, Leonid Gorelik2, Stephen D. Hurst3, Robert L. Coffman4, Richard A. Flavell2, and Fiona Powrie1

1 Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, England, UK
2 Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06520
3 Department of Immunology, Genentech, South San Francisco, CA 94080
4 Dynavax Technologies Corporation, Berkeley, CA 94710

CORRESPONDENCE Fiona Powrie: fiona.powrie{at}path.ox.ac.uk

CD4+CD25+ regulatory T (T reg) cells play a pivotal role in control of the immune response. Transforming growth factor-ß (TGF-ß) has been shown to be required for T reg cell activity; however, precisely how it is involved in the mechanism of suppression is poorly understood. Using the T cell transfer model of colitis, we show here that CD4+CD45RBhigh T cells that express a dominant negative TGF-ß receptor type II (dnTßRII) and therefore cannot respond to TGF-ß, escape control by T reg cells in vivo. CD4+CD25+ T reg cells from the thymus of dnTßRII mice retain the ability to inhibit colitis, suggesting that T cell responsiveness to TGF-ß is not required for the development or peripheral function of thymic-derived T reg cells. In contrast, T reg cell activity among the peripheral dnTßRII CD4+CD25+ population is masked by the presence of colitogenic effector cells that cannot be suppressed. Finally, we show that CD4+CD25+ T reg cells develop normally in the absence of TGF-ß1 and retain the ability to suppress colitis in vivo. Importantly, the function of TGF-ß1–/– T reg cells was abrogated by anti–TGF-ß monoclonal antibody, indicating that functional TGF-ß can be provided by a non–T reg cell source.

Abbreviations used: dnTßRII, dominant negative TGF-ß receptor II; LP, lamina propria; Tg, transgenic; T reg, regulatory T.

L. Fahlén and S. Read contributed equally to this work.


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 Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Refusing to be suppressed
Heather L. Van Epps
J. Exp. Med. 2005 201: 663. [Full Text] [PDF]



This article has been cited by other articles:



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