Natural killer cell responses to dendritic cells infected by the ANRS HIV-1 vaccine candidate, MVAHIV

Abstract Innate mechanisms are critical for the development of the host immune responses to antigen. Particularly, early interaction between natural killer (NK) cells and dendritic cells (DC) greatly impacts the establishment of both innate and adaptive immune responses. In this study, using an autologous in vitro co-culture system we analyzed the NK cell response against MVA HIV -infected DC as well as the subsequent ability of these MVA HIV -primed NK cells to control HIV-1 infection in autologous DC. We found that NK cells responded early to MVA HIV - or MVA WT -infected DC in terms of degranulation and cytokine production. After a 4-day priming of NK cells by MVA HIV - or MVA WT -infected DC we observed an enhanced proliferation and modulation in the NK cell receptor repertoire expression. Interestingly, we found that MVA HIV -primed NK cells had a significant higher ability to control HIV-1 infection in autologous DC compared to MVA WT -primed NK cells; and this enhanced anti-HIV-1 activity appeared to be HIV-specific as MVA HIV -primed NK cells did not have a better ability to control other viral infections or respond against tumoral cells. Furthermore, we observed that NK cell receptors NKG2D and NKp46 modulate the priming of NK cells. This data provides evidence that in vitro NK cells can be primed by viral vector-infected DC, in the context of a NK/DC culture, to specifically target viral infected cells.