KIR down-regulation on NK cells is associated with down-regulation of activating receptors and NK cell inactivation.
We previously reported that killer cell immunoglobulin-like receptors (KIR) could be down-regulated from the surface of T cells. Here, we show that KIR down-regulation is also induced on the surface of natural killer (NK) cells upon ligand binding. Common down-regulation characteristics are found on these two cell types: a slow kinetics and a phenomenon observed for long inhibitory forms only. Importantly, KIR down-regulation on NK cells is associated with a down-regulation of activating receptors (CD16, CD2 and 2B4) as well as with a lack of cell responsiveness (antibody-dependent and natural killing activities). This unresponsive state was not observed for MHC-restricted T cells. Our data implicate that, in addition to prevention of the immediate target cell lysis, KIR-MHC class I interactions may also regulate the subsequent NK cell cytotoxic activity. This observation opens new perspectives in the understanding of NK cell regulation.
Huard
B
B
Laboratoire d'Immunologie des Tumeurs, Université Paris-Sud, Chatenay Malabry, France. huard@omu.unige.ch
Karlsson
L
L
Triebel
F
F
D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D015236:HLA-C Antigens / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D054340:Receptors, KIR
D015236:HLA-C Antigens; D011971:Receptors, Immunologic; D054340:Receptors, KIR