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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3254-3263. Prepublished online as a Blood First Edition Paper on October 23, 2008; DOI 10.1182/blood-2008-07-168906. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2008-07-168906v1 113/14/3254    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Taghon, T. Articles by Plum, J. Search for Related Content PubMed PubMed Citation Articles by Taghon, T. Articles by Plum, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 15, 2008 Accepted October 7, 2008 Notch signalling is required for proliferation but not for differentiation at a well-defined -selection checkpoint during human T cell development Tom Taghon*, Inge Van de Walle, Greet De Smet, Magda De Smedt, Georges Leclercq, Bart Vandekerckhove, and Jean Plum The Department of Clinical Chemistry, Microbiology and Immunology, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium * Corresponding author; email: tom.taghon{at}ugent.be. Notch signalling is absolutely required for -selection during mouse T cell development, both for differentiation and proliferation. In this report, we investigated whether Notch has an equally important role during human T cell development. We show that human CD34+ thymocytes can differentiate into CD4+CD8+ double positive (DP) thymocytes in the absence of Notch signalling. While these DP cells phenotypically resemble human -selected cells, they lack a TCR--chain. Therefore, we characterised the -selection checkpoint in human T cell development, using CD28 as a differential marker at the immature single positive CD4+CD3-CD8- stage. Through intracellular TCR- staining and gene expression analysis, we show that CD4+CD3-CD8-CD28+ thymocytes have passed the -selection checkpoint, in contrast to CD4+CD3-CD8-CD28- cells. These CD4+CD3-CD8-CD28+ thymocytes can efficiently differentiate into CD3+TCR+ human T cells in the absence of Notch signalling. Importantly, pre-selection CD4+CD3-CD8-CD28- thymocytes can also differentiate into CD3+TCR+ human T cells without Notch activation when provided with a rearranged TCR- chain. Proliferation of human thymocytes, however, is clearly Notch-dependent. Thus, we have characterised the -selection checkpoint during human T cell development and show that human thymocytes require Notch signalling for proliferation but not for differentiation at this stage of development. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: I. Van de Walle, G. De Smet, M. De Smedt, B. Vandekerckhove, G. Leclercq, J. Plum, and T. Taghon An early decrease in Notch activation is required for human TCR-{alpha}{beta} lineage differentiation at the expense of TCR-{gamma}{delta} T cells Blood, March 26, 2009; 113(13): 2988 - 2998. [Abstract] [Full Text] [PDF]

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