The activating receptor, NKp30, is important in the interactions between rat natural killer cells and dendritic cells (102.20)

Abstract

Abstract There is considerable interest in using dendritic cells (DC) to induce transplant tolerance. DC and natural killer (NK) cells have been found to interact in a bi-directional manner. DCs can activate human NK cells to more effectively kill, while NK cells can mediate both maturation and killing of DCs via an NK cell activation receptor, NKp30. NK cells expressing this receptor are elevated post-transplantation prompting us to examine NK cell interactions with DC in a rodent experimental system. Wildtype and rNKp30-transfected RNK-16 cells (rat NK cell line) were co-cultured with bone marrow-derived DCs (BMDC). There was a significant increase in IFNγ production when rNKp30+, but not rNKp30−, NK cells were co-cultured with both immature and mature BMDCs. This NK-DC interaction required cell contact. Flow cytometric analysis of BMDCs with the rNKp30-Fc fusion protein (as compared to a control Fc fusion protein) indicated the presence of rNKp30 ligand(s) on the surface of DCs. Several tumor cell lines also specifically bound rNKp30-Fc. rNKp30-Fc binding was abolished by pretreatment of the tumor cells with trypsin suggesting the ligand is a protein. Furthermore, we established that the expression level of putative rNKp30 ligands correlated with the ability to activate NK cells, as indicated by the levels of IFNγ. Understanding NK cell interactions with DC may suggest potential new targets for tolerance induction.