Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide

Madera, Sharline; Rapp, Moritz; Firth, Matthew A.; Beilke, Joshua N.; Lanier, Lewis L.; Sun, Joseph C.

We explored two possibilities for the expansion defect of Ifnar −/− NK cells in response to MCMV infection: proliferation and apoptosis. To investigate whether a proliferative defect exists in NK cells that are unable to sense type I IFNs, cell trace violet (CTV)-labeled Ly49H + NK cells from WT :Ifnar − /− chimeras were transferred into Ly49H-deficient hosts and infected with MCMV. Ifnar −/− NK cells exhibited a modest increase in proliferation when compared with WT NK cells at day 4 PI (Fig. 4 A) , suggesting that type I IFN signals actually restrain NK cell proliferation after activation. We next compared the amount of apoptosis in Ifnar −/− and WT NK cells that are activated during MCMV infection. After adoptive transfer and MCMV infection, Ifnar −/− NK cells incorporated significantly more fluorescent-labeled inhibitor of caspases (FLI CA), a measurement of activated caspases, than WT NK cells at day 4 PI (Fig. 4 B; 2.1 ± 0.5% vs. 12.0 ± 1.8%, respectively; P = 0.006). Together, these findings suggest that type I IFNs shield activated NK cells from cell death during viral infection.