Individual heterogeneity determines the interaction between human dendritic cells and natural killer cells (147.23)

Abstract

Abstract Previous research has shown that human dendritic cells (DC) can promote activation of natural killer cells (NK), including IFN-γ secretion and enhanced expression of activation markers. However, our recent research suggests that the heterogeneity of individual human donors determines the effect of DC on NK. In our experiments, DC, generated from peripheral blood monocytes and matured by LPS, were co-cultured with autologous NK cells purified from peripheral blood for 24 hours. In the 31 samples, only two donors’ mature DC significantly promoted the secretion of IFN-γ by NK. DC from an additional ten donors promoted the secretion of IFN-γ in the presence of a very low dosage IL-2 or IL-15 which by themselves had no effect. However, all DC could increase expression of CD69 on NK to varying degrees. Further, the DC, not the NK cells, were the key factor for increased IFN-γ secretion because those DC with higher ability to activate autologous NK could also activate allogeneic NK which had otherwise failed to be stimulated with their own autologous DC. Moreover, our current samples did not suggest that the age of the donor was significant for the interaction of NK and DC. Since both NK and DC are very important in infectious disease and cancer immunology, the heterogeneity of NK and DC crosstalk might be related to the susceptibility of some individuals to infection and cancer. However, the mechanisms that determine the effect of DC on NK activation remain to be investigated.