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 language | English |
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Pages (from-to) | 2528-2540 |
Number of pages | 13 |
Journal | Cell Reports |
Volume | 21 |
Issue number | 9 |
DOIs | |
State | Published - Nov 28 2017 |
Keywords
- B cell
- LCMV
- NKG2A
- NKreg
- Qa-1b
- anti-viral T cell
- chronic viral infection