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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Elsevier 2017-11-01
• Series: Cell Reports
• Subjects: Qa-1b; NKG2A; NKreg; LCMV; anti-viral T cell; chronic viral infection; B cell
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717316042

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.