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Human CD34+ fetal liver stem cells differentiate to T cells in a mouse
thymic microenvironment
J Plum, M De Smedt, MP Defresne, G Leclercq and B Vandekerckhove
Department of Clinical Chemistry, Microbiology and Immunology, University
of Ghent, University Hospital, Belgium.
Hematopoietic stem cells differentiate in the thymus to T cells along
precisely defined intermediates. This process is thymic epithelium
dependent and involves cytokines and cell-cell interactions between thymic
stroma and T-cell precursors. Here we report that highly purified human
CD34++ fetal liver stem cells differentiate to mature T cells, when seeded
into isolated fetal thymic lobes of severe combined immunodeficient mice,
and subsequently cultured in vitro. The human stem cells differentiate
sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-, CD4+CD8+CD3+, and finally,
CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic analysis for additional
maturation markers showed that these CD4 and CD8 single-positive thymocytes
are fully maturate cells. By immunochemistry, human HLA-DR+ cells with a
dendritic morphology could be detected. This novel chimeric human-mouse
fetal thymus organ culture offers a tool to study human T-cell ontogeny in
vitro and is a rapid and reliable test method for T-cell precursor activity
of cultured or transfected human stem cells.
Volume 84,
Issue 5,
pp. 1587-1593,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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