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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 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 Citation Map 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. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Notch signaling is required for proliferation but not for differentiation at a well-defined β-selection checkpoint during human T-cell development Tom Taghon1, Inge Van de Walle1, Greet De Smet1, Magda De Smedt1, Georges Leclercq1, Bart Vandekerckhove1, and Jean Plum1 1 Department of Clinical Chemistry, Microbiology, and Immunology, Faculty of Medicine and Health Sciences, Ghent University, Ghent University Hospital, Ghent, Belgium Notch signaling is absolutely required for β-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+CD8β+ double positive (DP) thymocytes in the absence of Notch signaling. While these DP cells phenotypically resemble human β-selected cells, they lack a T-cell receptor (TCR)–β chain. Therefore, we characterized the β-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-β staining and gene expression analysis, we show that CD4+CD3–CD8–CD28+ thymocytes have passed the β-selection checkpoint, in contrast to CD4+CD3–CD8–CD28– cells. These CD4+CD3–CD8–CD28+ thymocytes can efficiently differentiate into CD3+TCRβ+ human T cells in the absence of Notch signaling. Importantly, preselection CD4+CD3–CD8–CD28– thymocytes can also differentiate into CD3+TCRβ+ human T cells without Notch activation when provided with a rearranged TCR-β chain. Proliferation of human thymocytes, however, is clearly Notch-dependent. Thus, we have characterized the β-selection checkpoint during human T-cell development and show that human thymocytes require Notch signaling 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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