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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3579-3587. Prepublished online as a Blood First Edition Paper on January 9, 2007; DOI 10.1182/blood-2006-08-039842. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-039842v1 109/8/3579    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 Dallas, M. H Articles by Bernstein, I. D Search for Related Content PubMed PubMed Citation Articles by Dallas, M. H Articles by Bernstein, I. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 7, 2006 Accepted December 6, 2006 Enhanced T cell reconstitution by hematopoietic progenitors expanded ex-vivo using the notch ligand delta1 Mari H Dallas, Barbara Varnum-Finney, Paul J Martin, and Irwin D Bernstein* Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA Department of Pediatrics, University of Washington, Seattle, WA * Corresponding author; email: ibernste{at}fhcrc.org. A physiologic role for Notch signaling in hematopoiesis has been clearly defined in lymphoid differentiation, with evidence suggesting a critical role in T cell versus B cell fate decisions. Previously, we demonstrated that activation of endogenous Notch receptors by culture of murine lin-Sca-1+c-kit+ (LSK) hematopoietic progenitors with exogenously presented Notch ligand, Delta1ext-IgG, consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG 1, promoted early T cell differentiation and increased the number of progenitors capable of short-term lymphoid and myeloid reconstitution. Here we show that culture of LSK precursors with Delta1ext-IgG increases the number of progenitors that are able to rapidly repopulate the thymus and accelerate early T cell reconstitution with a diversified T cell receptor repertoire. Most of the early T cell reconstitution originated from cells that expressed lymphoid associated antigens: B220, Thy1, CD25 and/or IL7R, whereas the most efficient thymic repopulation on a per cell basis originated from the smaller number of cultured cells that did not express lymphoid associated antigen. These findings demonstrate the potential of Delta1ext-IgG-cultured cells for accelerating early immune reconstitution after hematopoietic cell transplantation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Varnum-Finney, M. H. Dallas, K. Kato, and I. D. Bernstein Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus Blood, March 1, 2008; 111(5): 2615 - 2620. [Abstract] [Full Text] [PDF]

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