Immunity. 2014 Jun 4. pii: S1074-7613(14)00181-2. doi: 10.1016/j.immuni.2014.05.003. [Epub ahead of print]

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

Crouse J1, Bedenikovic G1, Wiesel M1, Ibberson M2, Xenarios I2, Von Laer D3, Kalinke U4, Vivier E5, Jonjic S6, Oxenius A7.

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Abstract

Direct type I interferon (IFN) signaling on T cells is necessary for the proper expansion, differentiation, and survival of responding T cells following infection with viruses prominently inducing type I IFN. The reasons for the abortive response of T cells lacking the type I IFN receptor (Ifnar1-/-) remain unclear. We report here that Ifnar1-/- T cells 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-/- T cells. Ifnar1-/- T cells 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 T cells protects them from NK cell killing by regulating the expression of NCR1 ligands, thereby revealing a mechanism by which T cells can evade the potent cytotoxic activity of NK cells.

Copyright © 2014 Elsevier Inc. All rights reserved.

PMID:
24909889