Type I Interferons Protect T Cells against NK Cell Attack Mediated by the Activating Receptor NCR1

Abstract

Direct type I interferon (IFN) signaling on Tcells is necessary for the proper expansion, differentiation, and survival of responding Tcells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of Tcells lacking the type I IFN receptor (Ifnar1(-/-)) remain unclear. We report here that Ifnar1(-/-) Tcells were highly susceptible to natural killer (NK) cell-mediated killing in a perforin-dependent manner. Depletion of NK cells prior to lymphocytic choriomeningitis virus (LCMV) infection completely restored the early expansion of Ifnar1(-/-) Tcells. Ifnar1(-/-) Tcells had elevated expression of natural cytotoxicity triggering receptor 1 (NCR1) ligands upon infection, rendering them targets for NCR1 mediated NK cell attack. Thus, direct sensing of type I IFNs by Tcells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which Tcells can evade the potent cytotoxic activity of NK cells.