In vitro intrathymic differentiation kinetics of human fetal liver CD34(+)CD38(-) progenitors reveals a phenotypically defined dendritic/T-NK precursor split

Human CD34(+)CD38(-) hematopoietic precursor cells from fetal liver are abl e 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 remaine d CD7(-)cyCD3(-)HLA-DR++ and a CD4(-) population that expressed CD7 and cyC D3. The CD4(+)CD7(-)cyCD3(-) cells differentiate into phenotypically and fu nctionally mature dendritic cells, but do not differentiate into T or NK ce lls. The CD4(-)CD7(+)cyCD3(+) population later differentiates into a CD4(+) CD7(+)cyCD3(+)HLA-DR- population, which has no potential to differentiate i nto dendritic cells but is able to differentiate into NK cells and gamma de lta and alpha beta T lymphocytes, These findings support the notion that th e T/NK split occurs downstream of the NK/dendritic split.