The Journal of Experimental Medicine
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 2 October 2006 doi:10.1084/jem.20060956
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 203, Number 11, 2451-2460
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 Yurchenko, E.
Right arrow Articles by Piccirillo, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yurchenko, E.
Right arrow Articles by Piccirillo, C. A.
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

 CCR5-dependent homing of naturally occurring CD4+ regulatory T cells to sites of Leishmania major infection favors pathogen persistence

Ekaterina Yurchenko1, Michael Tritt1, Valerie Hay1, Ethan M. Shevach3, Yasmine Belkaid4, and Ciriaco A. Piccirillo1,2

1 Department of Microbiology and Immunology and 2 Strategic Training Centre in Infectious Diseases and Autoimmunity, McGill University, Montreal, H3A 2B4, Canada
3 Laboratory of Immunology and 4 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892

CORRESPONDENCE Ciriaco A. Piccirillo: ciro.piccirillo{at}mcgill.ca

Pathogen persistence after clinical cure is a hallmark of many chronic infections. Previously, we showed that naturally occurring CD4+CD25+ regulatory T (nTreg) cells rapidly accumulate within chronic dermal sites of Leishmania major infection where they suppress anti-pathogen CD4+ T cell responses, favor parasite persistence and dermal pathology, and consequently control concomitant immunity. Here, we postulated that chemokines might direct nTreg cell homing in sites of infection and show that CD4+CD25+ nTreg cells, compared with normal CD4+ T cells, preferentially express the CCR5 chemokine receptor, which enables them to migrate in response to CCR5 ligands in vitro. We show that in contrast to their wild-type (WT) counterparts, CCR5–/– CD4+CD25+ nTreg cells resulted in an increased magnitude of parasite-specific, interferon {gamma}–producing CD4+ T cells within infection sites, dramatically reduced parasite numbers, and potent resistance to infection, a finding consistent with the clinical outcome of infected CCR5–/– mice. Interestingly, this resistance was related to an inefficient migration of CCR5–/– nTreg cells to infected dermal sites compared with WT nTreg cells. Thus, this study shows that CCR5 directs the homing of CD4+CD25+ nTreg cells to L. major–infected dermal sites where they promote the establishment of infection and long-term survival of the parasite in the immune host.

Abbreviations used: BMDC, bone marrow–derived dendritic cell; i.d., intradermal; nTreg, naturally occurring CD4+ regulatory T.


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?


This article has been cited by other articles:



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