Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 26 March 2009, Vol. 113, No. 13, pp. 2988-2998.
Prepublished online as a Blood First Edition Paper on December 3, 2008; DOI 10.1182/blood-2008-06-164871.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Table
Right arrow All Versions of this Article:
blood-2008-06-164871v1
113/13/2988    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Van de Walle, I.
Right arrow Articles by Taghon, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Van de Walle, I.
Right arrow Articles by Taghon, T.
Related Collections
Right arrow Immunobiology
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

IMMUNOBIOLOGY

An early decrease in Notch activation is required for human TCR-{alpha}β lineage differentiation at the expense of TCR-{gamma}{delta} T cells

Inge Van de Walle1, Greet De Smet1, Magda De Smedt1, Bart Vandekerckhove1, Georges Leclercq1, Jean Plum1, and Tom Taghon1

1 Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Ghent University Hospital, Ghent, Belgium

Although well characterized in the mouse, the role of Notch signaling in the human T-cell receptor {alpha}β (TCR-{alpha}β) versus TCR-{gamma}{delta} lineage decision is still unclear. Although it is clear in the mouse that TCR-{gamma}{delta} development is less Notch dependent compared with TCR-{alpha}β differentiation, retroviral overexpression studies in human have suggested an opposing role for Notch during human T-cell development. Using the OP9-coculture system, we demonstrate that changes in Notch activation are differentially required during human T-cell development. High Notch activation promotes the generation of T-lineage precursors and {gamma}{delta} T cells but inhibits differentiation toward the {alpha}β lineage. Reducing the amount of Notch activation rescues {alpha}β-lineage differentiation, also at the single-cell level. Gene expression analysis suggests that this is mediated by differential sensitivities of Notch target genes in response to changes in Notch activation. High Notch activity increases DTX1, NRARP, and RUNX3 expression, genes that are down-regulated during {alpha}β-lineage differentiation. Furthermore, increased interleukin-7 levels cannot compensate for the Notch dependent TCR-{gamma}{delta} development. Our results reveal stage-dependent molecular changes in Notch signaling that are critical for normal human T-cell development and reveal fundamental molecular differences between mouse and human.


Add to CiteULike CiteULike   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?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020