Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection

Haifeng C. Xu, Jun Huang, Aleksandra A. Pandyra, Elisabeth Lang, Yuan Zhuang, Christine Thöns, Jörg Timm, Dieter Häussinger, Marco Colonna, Harvey Cantor, Karl S. Lang, Philipp A. Lang

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13 Scopus citations

Abstract

NK cells can reduce anti-viral T cell immunity during chronic viral infections, including infection with the lymphocytic choriomeningitis virus (LCMV). However, regulating factors that maintain the equilibrium between productive T cell and NK cell immunity are poorly understood. Here, we show that a large viral load resulted in inhibition of NK cell activation, which correlated with increased expression of Qa-1b, a ligand for inhibitory NK cell receptors. Qa-1b was predominantly upregulated on B cells following LCMV infection, and this upregulation was dependent on type I interferons. Absence of Qa-1b resulted in increased NK cell-mediated regulation of anti-viral T cells following viral infection. Consequently, anti-viral T cell immunity was reduced in Qa-1b- and NKG2A-deficient mice, resulting in increased viral replication and immunopathology. NK cell depletion restored anti-viral immunity and virus control in the absence of Qa-1b. Taken together, our findings indicate that lymphocytes limit NK cell activity during viral infection in order to promote anti-viral T cell immunity. Xu et al. show that Qa-1b expression is predominantly upregulated on B lymphocytes following lymphocytic choriomeningitis virus infection. Absence of Qa-1b results in increased NK cell-mediated regulation of anti-viral T cells, limited anti-viral immunity, and chronic viral infection.

Original languageEnglish
Pages (from-to)2528-2540
Number of pages13
JournalCell Reports
Volume21
Issue number9
DOIs
StatePublished - Nov 28 2017

Keywords

  • B cell
  • LCMV
  • NKG2A
  • NKreg
  • Qa-1b
  • anti-viral T cell
  • chronic viral infection

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    Xu, H. C., Huang, J., Pandyra, A. A., Lang, E., Zhuang, Y., Thöns, C., Timm, J., Häussinger, D., Colonna, M., Cantor, H., Lang, K. S., & Lang, P. A. (2017). Lymphocytes Negatively Regulate NK Cell Activity via Qa-1b following Viral Infection. Cell Reports, 21(9), 2528-2540. https://doi.org/10.1016/j.celrep.2017.11.001