Human CD34+ fetal liver stem cells differentiate to T cells in a mouse thymic microenvironment.
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.
Plum
J
J
Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital, Belgium.
De Smedt
M
M
Defresne
M P
MP
Leclercq
G
G
Vandekerckhove
B
B
D000818:Animals; D015703:Antigens, CD / Q000032:analysis / Q000096:biosynthesis / Q000276:immunology*; D018952:Antigens, CD34; D015704:CD4 Antigens / Q000032:analysis / Q000096:biosynthesis; D016827:CD8 Antigens / Q000032:analysis / Q000096:biosynthesis; D002454:Cell Differentiation / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D005333:Fetus; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000196:embryology / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D009924:Organ Culture Techniques; D011247:Pregnancy; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology*
D015703:Antigens, CD; D018952:Antigens, CD34; D015704:CD4 Antigens; D016827:CD8 Antigens