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In Vitro Intrathymic Differentiation Kinetics of Human Fetal Liver CD34⁺CD38^- Progenitors Reveals a Phenotypically Defined Dendritic/T-NK Precursor Split¹

University of Ghent, University Hospital, Department of Clinical Chemistry, Microbiology and Immunology, Ghent, Belgium

Human CD34⁺CD38^- hematopoietic precursor cells from fetal liver are able to develop into T, NK, and dendritic cells in a hybrid human/mouse fetal thymic organ culture (FTOC). In this report, we pay particular attention to the early events in differentiation of these precursor cells. We show that the CD34⁺CD38^- precursor cells, which are CD4^-CD7^-cyCD3^-HLA-DR^-/++ (cy, cytoplasmatic), differentiate into a CD4⁺ population that remained CD7^-cyCD3^-HLA-DR⁺⁺ and a CD4^- population that expressed CD7 and cyCD3. The CD4⁺CD7^-cyCD3^- cells differentiate into phenotypically and functionally mature dendritic cells, but do not differentiate into T or NK cells. The CD4^-CD7⁺cyCD3⁺ population later differentiates into a CD4⁺CD7⁺cyCD3⁺HLA-DR^- population, which has no potential to differentiate into dendritic cells but is able to differentiate into NK cells and and ß T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.

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