Premium
Liver NK cells play an inhibitory role in impairing antiviral CD8+ T cell effector function
Author(s) -
Lukens John R.,
Dolina Joseph,
Hahn Young S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.856.5
Subject(s) - cytotoxic t cell , effector , cd8 , biology , immunology , t cell , interleukin 21 , antigen , immune system , in vitro , biochemistry
NK cells play a pivotal role in innate immunity to viral infection and linking to adaptive immunity. The liver is a tolerogenic site and often succumbs to persistent viral infection. To determine whether NK cells are responsible for influencing CD8+ T cell responses in the liver, we examined intrahepatic CD8+ T cell responses in mice following infection with recombinant adenovirus expressing LacZ antigen (Ad‐LacZ). Two different routes of Ad‐LacZ infection were employed which allowed for delivery of antigen into the liver or secondary lymphoid organs preferentially. Notably, CD8+ T cells primed in the liver exhibit significantly impaired effector function with inhibition of IFN‐γ, TNF‐α production and failure of viral clearance. The impairment of CD8+ T cell effector function in the liver was associated with the increased level of PD‐1 expression. In contrast, the liver was able to sustain CD8+ T cell effector function when these CD8+ T cells were primed in secondary lymphoid organ. Surprisingly, the in vivo depletion of NK cells in Ad‐LacZ‐infected mice restored the impaired CD8+ T cell responses primed in the liver environment. These results suggest that liver NK cells are crucial for modulating CD8+ T cell effector activity in the liver.