The effect of silencing NKG2D through RNA interference on receptor functions in interleukin-2-activated human natural killer cells.
Natural killer (NK) cells are effectors of the innate immunity involved in tumor surveillance. NKG2D is a potent activating receptor eliciting cytokine and cytolytic NK responses upon recognition of tumor-associated ligands. We engineered primary interleukin (IL)-2-activated human NK cells to express constitutively low levels of NKG2D by lentiviral delivery of small interfering RNA. NKG2D-mediated effector functions were strongly impaired in NKG2D(low) NK cells. Reduction of NKG2D surface expression to 15%, corresponding to receptor levels in resting NK cells, rendered cells fully insensitive to NKG2D triggering. These data underscore the importance of NKG2D receptor cell surface density and suggest a threshold of expression for optimal reactivity of human NK cells.
Baeriswyl
Vanessa
V
Experimental Hematology, Department of Research, University Hospital Basel, Switzerland.
Wodnar-Filipowicz
Aleksandra
A
Kalberer
Christian P
CP
D002478:Cells, Cultured; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics*; D015979:Killer Cells, Lymphokine-Activated / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D034622:RNA Interference / Q000502:physiology*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000502:physiology; D055607:Receptors, Natural Killer Cell
D007376:Interleukin-2; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell