FETAL LIVER CONTAINS COMMITTED NK PROGENITORS, BUT IS NOT A SITE FOR DEVELOPMENT OF CD34(-CELLS() CELLS INTO T)

The presence of T and NK cells in the human fetal liver and the fact t hat fetal liver hemopoietic progenitor cells develop into T and NK cel ls suggest a role for the fetal liver compartment in T and NK cell dev elopment, In this work, we show that the capacity of fetal liver proge nitors to develop into T cells, in a human/mouse fetal thymic organ cu lture system, is restricted to an immature subset of CD34(+)CD38(-) ce lls, No T cell-committed precursors are contained within the more diff erentiated CD34(+)CD38(+) population, This conclusion is supported by the observations that no TCR-delta gene rearrangements and no pre-TCR- alpha expression can be detected in this population, However, NK cells were derived from CD34(+)CD38(-) and CD34(+)CD38(+) fetal liver cells cultured in the presence of IL-15, IL-7, and Flt-3 ligand, Eighty to ninety percent of cells arising from the CD34(+)CD38(+) population exp ressed the NK cell-associated markers CD56, CD16, CD94 and NKR-P1A, Se veral subpopulations of NK cell precursors were identified by differen tial expression of these receptors, Based on the detection of populati ons with a similar antigenic profile in freshly isolated fetal liver c ells, we propose a model of NK cell differentiation. Collectively, our findings suggest that CD34(+) cells differentiate into NK cells, but not into mature T cells, in the human fetal liver.