Abstract EN:

In early h, decidual NK s (dNK) are abundant and considered as cytokine producers but poorly cytotoxic despite their cytolytic granule content, suggesting a negative control of this latter effector function. Decidual NK cells express a large panel of activating and inhibitory receptors. However, little is known about the contribution of the different receptors expressed by dNK cells, to the cytotoxic function. The purpose of our study was to investigate the implication of activating and inhibitory receptors in the effector function of dNK cells and to investigate how these functions are regulated. We first found that freshly isolated dNK, in contrast to peripheral blood NK cells, exhibit a unique repertoire of activating and inhibitory receptors, identical among all the donors tested. We then demonstrated that in freshly isolated dNK, mAb-specific engagement of NKp46- and to a lesser extent NKG2C-, but not NKp30-activating receptors induced intracellular calcium mobilization, perforin polarization, granule exocytosis and efficient target cell lysis. NKp46-mediated cytotoxicity is co-activated by CD2 but dramatically blocked by NKG2A (inhibitory receptor) co-engagement, indicating that the dNK cytotoxic potential could be tightly controlled in vivo. Such NKG2A-mediated inhibition might be critical for the outcome of pregnancy. Finally, we found that in dNK, mAb-specific engagement of NKp30, but not NKp46, triggered the production of proinflammatory molecules (such as IFNgamma. . . ). We hypothesized that during pregnancy complications (viral infection), NKG2A-mediated inhibition could be prevented, and thus dNK cells could participate to the elimination of viral infected cells. We indeed found that dNK cells in contact with hCMV-infected fibroblasts proliferate, polarize their cytolytic granules to the immune synapse and kill infected target cells.