Adoptive transfer and pulmonary homing of NK cells rescues NK cell-deficient mice from early lethality during acute influenza A virus infection (130.11)

Abstract

Abstract Natural Killer (NK) cells are vital components of the innate antiviral immune response. NK cells are widely distributed, including the lung (comprising 5-10% of mononuclear cells). We have shown that anti-NK1.1-mediated depletion of NK cells in C57Bl/6 or recombinant-congenic BALB.B6-CT6 mice results in early morbidity and increased mortality to mouse-adapted influenza A virus (IAV), similar to that reported for Ncr1-deficient mice lacking the NKp46 receptor. Adoptive IV transfer of resting CFSE-labeled NK cells prepared from spleen or lung results in pulmonary NK cell reconstitution, with a striking preferential homing of pulmonary NK cells to lung compared to splenic NK cells. NK cell-reconstituted mice are comparable to NK cell-replete controls in morbidity and mortality to acute IAV infection, indicating that adoptive NK cell transfer mediates protection. Future experiments will test the protective capacity of adoptively transferred NK cells deficient in NK cell effector functions (IFN-γ, perforin, TRAIL, or FasL) during acute IAV infection. This novel system will expand our understanding of how NK cells populate the lung and contribute toward early anti-influenza virus immunity.