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

Autor: 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
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Cell Reports, Vol 21, Iss 9, Pp 2528-2540 (2017)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2017.11.001
Popis: 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.
Databáze: Directory of Open Access Journals