The chemokine CX3CL1 regulates NK cell activity in vivo

In vitro, chemokines can both activate and induce migration of NK cells. However, little is known about how chemokines influence NK cell activity in vivo. We studied the role of CX3CL1 and its receptor, CX3CR1, in modulating NK cell activity in an established in vivo model of tumour cell clearance. Radiolabelled YAC-1 target cells intravenously injected into C57BL/6 mice rapidly localize to the lungs and are cleared by NK cells. In mice pre-treated with blocking anti-CX3CL1 or anti-CX3CR1 Ab, target cell clearance decreased by four- to fivefold (p<0.001). In vitro, we found no effect of anti-CX3CL1 or anti-CX3CR1 Ab on NK lysis of target cells. We further examined adhesion of NK cells to Py-4-1 endothelial cells. NK cell binding to activated endothelial monolayers was significantly inhibited by anti-CX3CR1 Ab or soluble CX3CL1 (p<0.001). These studies identify a critical role for CX3CL1 in modulating NK cell activity in vivo.