IDENTIFICATION OF A COMMON DEVELOPMENTAL PATHWAY FOR THYMIC NATURAL-KILLER-CELLS AND DENDRITIC CELLS

Current data support the notion that the thymus is seeded by a yet unc ommitted progenitor cell able to generate T cells, B cells, natural ki ller (NK) cells, and dendritic cells (DCs). We assess in this report t he developmental relationship of DCs and NK cells derived from a small subset of CD34(+) human postnatal thymocytes that, like the earliest precursors in the fetal thymus, display low CD33 surface expression. C ulture of these isolated CD34(+) CD33(lo) thymic progenitors with a mi xture of cytokines, including interleukin-7 (IL-7), IL-1 alpha, IL-6, granulocyte-macrophage colony-stimulating factor, and stem cell factor , results in predominant generation of DCs, However, the addition of I L-2 to the cytokine mixture leads to the simultaneous development of D Cs and NK cells. Both developmental pathways progress through a transi ent population of CD34(+)CD44(bright) CD5(lo/-)CD33(+) large-sized cel ls, distinct from small-sized T-lineage precursors, that contain bipot ential NK/DC progenitors. These data provide evidence of linked pathwa ys of NE cell and DC development from intrathymic precursors and sugge st that NK cells and DCs branch off the T lineage through a common int ermediate progenitor, (C) 1998 by The American Society of Hematology.