Effect of interleukin-15 and Flt3-ligand on natural killer cell expansion and activation: Umbilical cord vs. adult peripheral blood mononuclear cell

Expansion and activation of cord blood (CB) natural killer (NK) cells by cytokines might greatly benefit patients undergoing stem cell transplantation by increasing resistance against viral infections and providing graft-vs.-leukemia (GVL) effects through enhanced cytolytic abilities. We tested the ability of a recently cloned stem cell factor, Flt3-ligand (Flt3L), in combination with interleukin-15 (IL-15), to stimulate CB mononuclear cells (MNCs) to proliferate and differentiate into NK cells, in comparison with adult peripheral blood (APB) MNCs. Unstimulated CB MNCs had low NK and lymphokine-activated killer (LAK) activity compared with APB MNCs. A similar dose-dependent increase in NK and LAK activity and CD16/56 expression was found with IL-15 in CB and APB MNCs after 10 days of culture. The NK cytotoxicity (against K562 cells) of IL-15-treated CB MNCs was lower than that of corresponding APB MNCs, while IL-15-induced LAK activity (against Daudi cells) of CB MNCs was comparable to that of corresponding APB MNCs. IL-15 resulted in greater CD16/56 expression in CB MNCs compared with APB MNCs after 10 days of culture. Flt3L, alone or in combination with IL-15, had little effect on CD16/56 expression and cytotoxicity. Cytotoxic activities and CD16/56 expression did not alter after CD34 depletion of CB MNCs. We therefore concluded that CB NK cells could be greatly activated and expanded with IL-15, but not with Flt3L. The greater expression of CD16/56 induced by IL-15 in CB MNCs may originate from non-CD34⁺ NK progenitor cells.