Targeting of human dendritic cells by autologous NK cells

NK cells have the capacity to spontaneously kill tumor cell lines, in parti cular cell lines of hemopoietic origin. In contrast, they do not generally kill nontransformed autologous cells. However, here we demonstrate that sho rt-term activated polyclonal human NK cells, as well as human NK cell lines , effeciently lyse autologous dendritic cells (DC) derived from peripheral blood monocytes as well as Langerhans-like cells derived from CD34(+) stem cells isolated from umbilical cord blood. Lysis of autologous DC by short-t erm activated NK cells and NK cell lines was dependent on granule exocytosi s, since total abrogation of lysis was observed in the presence of EGTA. In duction of DC maturation by LPS, monocyte conditioned media (MCM), or stimu lation through CD40 ligand (CD40L) rendered the DC less susceptible to lysi s by NK cells. Infection of DC with influenza virus was likewise associated with a reduced susceptibility to lysis by NK cells, Thus, susceptibility t o lysis by autologous NK cells is a particular property of immature DC. The present results are discussed in relation to the ability of DC to interact with NK cells and to the ability of NK cells to regulate development of sp ecific immunity.