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 CX(3)CL1 and its receptor, CX(3)CR1, 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-CX(3)CL1 or anti-CX(3)CR1 Ab, target cell clearance decreased by four- to fivefold (p<0.001). In vitro, we found no effect of anti-CX(3)CL1 or anti-CX(3)CR1 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-CX(3)CR1 Ab or soluble CX(3)CL1 (p<0.001). These studies identify a critical role for CX(3)CL1 in modulating NK cell activity in vivo.
Robinson
Lisa A
LA
The Hospital for Sick Children Research Institute, and the University of Toronto, Toronto, Canada. lisa.robinson@sickkids.ca
Nataraj
Chandra
C
Thomas
Dennis W
DW
Cosby
Josette M
JM
Griffiths
Robert
R
Bautch
Victoria L
VL
Patel
Dhavalkumar D
DD
Coffman
Thomas M
TM
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion / Q000276:immunology / Q000502:physiology; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism*; D008175:Lung Neoplasms / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515539:Cx3cl1 protein, mouse; D008565:Membrane Proteins; D012333:RNA, Messenger