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Blood, 30 July 2009, Vol. 114, No. 5, pp. 972-982. Prepublished online as a Blood First Edition Paper on June 2, 2009; DOI 10.1182/blood-2008-10-187013. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-10-187013v1 114/5/972    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 CrossRef Google Scholar Articles by Awong, G. Articles by Zúñiga-Pflücker, J. C. PubMed PubMed Citation Articles by Awong, G. Articles by Zúñiga-Pflücker, J. C. Related Collections Hematopoiesis and Stem Cells Immunobiology Transplantation Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Characterization in vitro and engraftment potential in vivo of human progenitor T cells generated from hematopoietic stem cells Génève Awong1, Elaine Herer2, Charles D. Surh3, John E. Dick4, Ross N. La Motte-Mohs1, and Juan Carlos Zúñiga-Pflücker1 1 Department of Immunology, University of Toronto, and Sunnybrook Research Institute, Toronto, ON; 2 Sunnybrook Health Sciences Centre, Perinatal and Gynaecology Program, Women's College Hospital Campus, Toronto, ON; 3 The Scripps Research Institute, Department of Immunology & Microbial Science, La Jolla, CA; and 4 Division of Cell and Molecular Biology, University Health Network, Toronto, ON T-cell development follows a defined set of stage-specific differentiation steps. However, molecular and cellular events occurring at early stages of human T-cell development remain to be fully elucidated. To address this, human umbilical cord blood (UCB) hematopoietic stem cells (HSCs) were induced to differentiate to the T lineage in OP9-DL1 cocultures. A developmental program involving a sequential and temporally discrete expression of key differentiation markers was revealed. Quantitative clonal analyses demonstrated that CD34+CD38– and CD34+CD38lo subsets of UCB contain a similarly high T-lineage progenitor frequency, whereas the frequency in CD34+CD38+/hi cells was 5-fold lower. Delta-like/Notch-induced signals increased the T-cell progenitor frequency of CD34+CD38–/lo cells differentiated on OP9-DL1, and 2 distinct progenitor subsets, CD34+CD45RA+CD7++CD5–CD1a– (proT1) and CD34+CD45RA+CD7++CD5+CD1a– (proT2), were identified and their thymus engrafting capacity was examined, with proT2 cells showing a 3-fold enhanced reconstituting capacity compared with the proT1 subset. Furthermore, in vitro–generated CD34+CD7++ progenitors effectively engrafted the thymus of immunodeficient mice, which was enhanced by the addition of an IL-7/IL-7 antibody complex. Taken together, the identification of T-progenitor subsets readily generated in vitro may offer important avenues to improve cellular-based immune-reconstitution approaches. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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