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

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Abstract
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 γδ and αβ T lymphocytes. These findings support the notion that the T/NK split occurs downstream of the NK/dendritic split.