The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 17 December 2001. doi:10.1084/jem.194.12.1875
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 234K)
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 Henning, G.
Right arrow Articles by Förster, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Henning, G.
Right arrow Articles by Förster, R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
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, 0022-1007/2001/12/1875/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 12, December 17, 2001 1875-1881

Brief Definitive Report

CC Chemokine Receptor 7–dependent and –independent Pathways for Lymphocyte Homing : Modulation by FTY720



Golo Henning1, Lars Ohl1, Tobias Junt2, Phillip Reiterer3, Volker Brinkmann4, Hideki Nakano5, Werner Hohenberger1, Martin Lipp3 and Reinhold Förster1

1 Section of Experimental Surgery and Immunology, University Clinic for Surgery and Nikolaus-Fiebiger-Zentrum, 91054 Erlangen, Germany
2 Institute for Experimental Immunology, Department of Pathology, University Hospital, CH-8091 Zürich, Switzerland
3 Max-Delbrück-Center for Molecular Medicine, 13092 Berlin, Germany
4 Novartis Pharma AG, CH-4002 Basel, Switzerland
5 Department of Immunology, Toho University School of Medicine, Ota-Ku, Tokyo 143-8540, Japan

Address correspondence to Prof. Dr. Reinhold Förster at his present address, Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Phone: 49-511-532-0; E-mail: reinhold.forster{at}web.de

Cognate interaction of chemokine receptor CCR7 on lymphocytes with its ligands CCL19 and CCL21 expressed on high endothelial venules (HEVs) is essential for effective migration of T and B cells across HEVs into secondary lymphoid organs. Plt mice, which lack expression of CCL19 and CCL21-ser, both ligands for CCR7 on HEVs, as well as CCR7-deficient mice, have a defective cell migration and reduced homing of lymphocytes. FTY720, a novel immunosuppressant, causes a reduction of lymphocytes in peripheral blood and tissues and their sequestration into lymphoid tissues. In this study we demonstrate that FTY720 rescues the homing defect in both CCR7-/- mice and plt mice. After FTY720 treatment, the number of CD4+ and CD8+ T cells as well as B cells in peripheral blood is reduced while pertussis toxin–sensitive homing into peripheral lymph nodes, mesenteric lymph node, and Peyer's patches is increased. Immunohistology demonstrates that FTY720 enables these cells to enter lymphoid tissue through HEVs. Thus, our data suggest an alternative G-{alpha}i-dependent, CCR7-CCL19/CCL21-independent mechanism for lymphocyte homing through HEVs which is strongly augmented in the presence of FTY720.

Key Words: lymphocyte migration • chemokine receptor • T cell • B cell • lymphoid organs


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