The Journal of Experimental Medicine
Fluorescence In Vivo Endomicroscopy
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 20 September 2004. doi:10.1084/jem.20040774
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 200, Number 6, 725-735
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 493K)
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 Rivino, L.
Right arrow Articles by Geginat, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rivino, L.
Right arrow Articles by Geginat, J.
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?
Chemokine Receptor Expression Identifies Pre–T Helper (Th)1, Pre–Th2, and Nonpolarized Cells among Human CD4+ Central Memory T Cells

Laura Rivino, Mara Messi, David Jarrossay, Antonio Lanzavecchia, Federica Sallusto, and Jens Geginat

Institute for Research in Biomedicine, 6500 Bellinzona, Switzerland

Address correspondence to Jens Geginat, Institute for Research in Biomedicine, Via Vela 6, 6500 Bellinzona, Switzerland. Phone: 41-91-8200313; Fax: 41-91-8200305; email: jens.geginat{at}irb.unisi.ch

We previously reported that central–memory T cells (TCM cells), which express lymph node homing receptors CCR7 and CD62L, are largely devoid of effector functions but acquire characteristics of effector–memory T cells (TEM cells) (i.e., CCR7– T helper [Th]1 or Th2 cells) after stimulation with T cell receptor agonists or homeostatic cytokines. Here we show that three chemokine receptors identify functional subsets within the human CD4+ TCM cell pool. TCM cells expressing CXCR3 secreted low amounts of interferon {gamma}, whereas CCR4+ TCM cells produced some interleukin (IL)-4, but not IL-5. In response to IL-7 and IL-15, CXCR3+ TCM and CCR4+ TCM cells invariably generated fully differentiated CCR7– Th1 and Th2 cells, respectively, suggesting that they represent pre-Th1 and pre-Th2 cells. Conversely, CXCR5+ TCM cells lacking CXCR3 and CCR4 remained nonpolarized and retained CCR7 and CD62L expression upon cytokine-driven expansion. Unlike naive cells, all memory subsets had a low T cell receptor rearrangement excision circle content, spontaneously incorporated bromodeoxyuridine ex vivo, and contained cells specific for tetanus toxoid. Conversely, recall responses to cytomegalovirus and vaccinia virus were largely restricted to CXCR3+ TCM and TEM cells. We conclude that antigen-specific memory T cells are distributed between TEM cells and different subsets of TCM cells. Our results also explain how the quality of primary T cell responses could be maintained by TCM cells in the absence of antigen.

Key Words: T cell subsets • memory maintenance • cytokines • differentiation • chemokine receptors

L. Rivino, M. Messi, and D. Jarrossay contributed equally to this work.

Abbreviations used in this paper: BrdU, bromodeoxyuridine; CFSE, carboxyfluorescein succinimidyl ester; PdBu, phorbol-12-13-dibutyrate; TCM cell, central–memory T cell; TEM cell, effector–memory T cell; TREC, T cell receptor rearrangement excision circle; TSST, toxic shock syndrome toxin; TT, tetanus toxoid; VV, vaccinia virus.


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