Adult, but not neonatal, human lymphoid progenitors respond to TLR9 ligation by producing functional NK-like cells.

Remarkable progress has been made in characterizing factors controlling lineage fate decisions of primitive progenitors that initiate the lymphoid program in bone marrow. However, the understanding of neonatal/adult differences in environmental signals that influence differentiation pathway stability is still incomplete. Our recent findings suggest that Toll-like receptors provide a mechanism for producing cells of the innate immune system from early stages of lymphoid development in mice. We now show that both human early multilymphoid progenitors and more differentiated lymphoid progenitors from normal adult bone marrow express TLR9. Furthermore, they respond to its ligation by upregulating the expression of IL-15Rβ (CD122) and accelerating the production of functional natural killer (NK)-like cells. Proliferation of the presumed equivalent progenitor cells from umbilical cord blood was stimulated by CpG-containing oligonucleotides or herpes simplex virus, but the already robust NK-cell formation was unchanged. This new information adds to other known differences between neonatal and adult lymphoid progenitors and suggests only the latter replenish innate NK-like cells in response to Toll-like receptor agonists.