The Inhibitory Receptor NKG2A Sustains Virus-Specific CD8+ T Cells in Response to a Lethal Poxvirus Infection

Aaron S. Rapaport, Jill Schriewer, Susan Gilfillan, Ed Hembrador, Ryan Crump, Beatrice F. Plougastel, Yaming Wang, Gaelle Le Friec, Jian Gao, Marina Cella, Hanspeter Pircher, Wayne M. Yokoyama, R. Mark L. Buller, Marco Colonna

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

CD8+ T cells and NK cells protect from viral infections by killing virally infected cells and secreting interferon-γ. Several inhibitory receptors limit the magnitude and duration of these anti-viral responses. NKG2A, which is encoded by Klrc1, is a lectin-like inhibitory receptor that is expressed as a heterodimer with CD94 on NK cells and activated CD8+ T cells. Previous studies on the impact of CD94/NKG2A heterodimers on anti-viral responses have yielded contrasting results and the in vivo function of NKG2A remains unclear. Here, we generated Klrc1-/- mice and found that NKG2A is selectively required for resistance to ectromelia virus (ECTV). NKG2A functions intrinsically within ECTV-specific CD8+ T cells to limit excessive activation, prevent apoptosis, and preserve the specific CD8+ T cell response. Thus, although inhibitory receptors often cause T cell exhaustion and viral spreading during chronic viral infections, NKG2A optimizes CD8+ T cell responses during an acute poxvirus infection.

Original languageEnglish
Pages (from-to)1112-1124
Number of pages13
JournalImmunity
Volume43
Issue number6
DOIs
StatePublished - 2015

Keywords

  • CD8 T cell
  • Cytokine
  • Inhibitory receptor
  • NK cell
  • NKG2A
  • Virus

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