NKG2A expression defines a subset of active NK cells in both murine and human immune system

Abstract

As an innate lymphocyte, natural killer (NK) cell is crucial for immune surveillance and resistance during influenza virus infection. In addition to its inhibitory role in NK cell function, here we demonstrated that NKG2A, accompanied with NKp46, could be used to define a novel spleen memory NK cell subset in influenza virus infected mice. This memory NKp46+NKG2A+ NK cell subset was hemagglutinin (HA) protein specific and exhibited function switch, which was characterized with loss of virus-specific cytotoxicity but increased production of interferon (IFN)-ppand tumor necrosis factor (TNF)-aaproduction. This function switch was dependent on HSP70-mediated pathway. Moreover, this memory NK cell subset shaped the viral clearance and responses of CD8+ T cell-mediated adaptive immunity during influenza virus re-challenge. NKG2A+ NK subset against influenza virus could also be found in human peripheral CD56dimCD16hi NK population and showed the increase of cytotoxicity to influenza virus-infected target cells compared with NKG2A- subset. Moreover, this NKG2A+ NK cell subset possessed higher proliferation and potential to differentiate into CD56hiCD16dim subpopulation after IL2 or IL15 stimulation. Our study supported the potential of NK cell-targeted treatments to improve the efficacy of prophylaxis and therapy strategy against influenza virus. More importantly, NKG2A-expressing NK cells might act as the effective target subset. Finally, NKG2A representing an active CD56dimCD16hi NK subset might help us improve understanding on the development and function of NK cells.