Type I interferons protect T cells against NK cell attack mediated by the activating receptor NCR1

Immunity. 2014 Jun 19;40(6):961-73. doi: 10.1016/j.immuni.2014.05.003. Epub 2014 Jun 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Ly / immunology*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Cells, Cultured
  • Cytotoxicity, Immunologic*
  • Immunity, Innate
  • Interferon Type I / immunology*
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation / immunology
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Cytotoxicity Triggering Receptor 1 / immunology*
  • Perforin / biosynthesis
  • Receptor, Interferon alpha-beta / genetics*
  • Rhabdoviridae Infections / immunology
  • Signal Transduction / immunology
  • Vesiculovirus / genetics
  • Vesiculovirus / immunology
  • Virus Replication / immunology


  • Antigens, Ly
  • Ifnar1 protein, mouse
  • Interferon Type I
  • Natural Cytotoxicity Triggering Receptor 1
  • Ncr1 protein, mouse
  • Perforin
  • Receptor, Interferon alpha-beta

Associated data

  • GEO/GSE57355