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, et al: Cell Reports, Volume 21, Issue 9, 28 November 2017, Pages 2528-2540 Read More

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. © 2017 The Authors

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Posted on November 30, 2017
Posted in: HPAN, Neurodegeneration, Neurogenetics & Transcriptomics, Publications Authors: