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Cell Rep. 2017 Nov 28;21(9):2528-2540. doi: 10.1016/j.celrep.2017.11.001.

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

Author information

1
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany.
2
Department of Gastroenterology, Hepatology, and Infectious Diseases, Heinrich-Heine-University Düsseldorf, 40225 Düsseldorf, Germany.
3
Institute for Virology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
4
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
5
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, Boston, MA 02115, USA.
6
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen 45147, Germany.
7
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, 40225 Düsseldorf, Germany. Electronic address: langp@uni-duesseldorf.de.

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.

KEYWORDS:

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

PMID:
29186689
DOI:
10.1016/j.celrep.2017.11.001
[Indexed for MEDLINE]
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