Natural Killer cell interactions with dendritic cells and tumor cells are mediated by different NK cell receptors (141.10)

Abstract

Abstract NK cells infiltrate solid organ allografts early post-transplant. As NK cells can mediate both maturation and killing of dendritic cells (DC), a better understanding of NK-DC interactions after transplant is warranted. This study investigates the interaction of NK cells with DC and tumor cells, and the specific NK cell activation receptors (NKRs) involved. A rat NK cell line was co-cultured with rat bone marrow-derived DC and rat hepatoma McA-RH7777 (McA). Co-culture of NK cells with DC and McA resulted in significant IFNγ production. This IFNγ production required cell contact suggesting that specific NKRs are involved. To specifically address this possibility, the NKRs, NKp30, NKp46, NKG2D, were knocked down using RNAi. NK cell activation by DC is mediated by NKp46 as knockdown of this receptor markedly decreased IFNγ production. In contrast, NKp30, not NKp46, was responsible for NK cell activation by tumor. Flow cytometry on DC and McA with NKR fusion proteins indicated the presence of putative ligands. Interestingly, individual NKR knockdown did not markedly diminish NK cell killing suggesting NK cells use multiple receptors and/or other mechanisms to kill cells. In conclusion, both DC and tumor activate NK cells but NKp46 and NKp30 mediate these interactions respectively. These data suggest a means to manipulate specific NK cell interactions after transplantation. Funding: NIH AI44095, and Agency for Science, Technology and Research (Singapore).