Reconstitution of dendritic and natural killer-cell subsets after allogeneic stem cell transplantation: effects of endogenous flt3 ligand

Abstract

Recovery of dendritic cells (DCs) and natural killer (NK) cells after allogeneic stem cell transplantation (SCT) is important for allograft responses and antitumor immunity and thus for treatment outcome. Regulation of this regenerative process is not well understood. We investigated the influence of endogenous cytokines on the recovery and diversification of DC and NK cell subsets up to 6 months after SCT. Reconstitution of circulating DCs and NK cells was rapid but accompanied by prolonged skewing of cell subsets. The speed of recovery of CD11c(+)CD123(low) DC1 exceeded that of CD11c(-) CD123(+) DC2, and correlated with plasma levels of flt3 ligand (FL), but not with granulocyte or granulocyte-macrophage colony-stimulating factors and stem cell factor. There was a 5-fold increase in interferon-gamma-producing CD56(high)CD16(-)/low NK cells and a corresponding reduction in the CD56(low)CD16(high) subset, accompanied by strongly reduced NK cell cytotoxicity. In vitro data implicate an inhibitory effect of cyclosporin A on NK cell differentiation and cytotoxicity. NK cell numbers did not correlate with plasma levels of FL or interleukin 15. Our results demonstrate that endogenous FL has distinct effects on the kinetics of reconstitution of DCs and NK cells and have potential implications for the modulation of immune responses after allogeneic SCT.