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Marquardt, Nicole; Béziat, Vivien; Nyström, Sanna; Hengst, Julia; Ivarsson, Martin A; Kekäläinen, Eliisa; Johansson, Helene; Mjösberg, Jenny; Westgren, Magnus; Lankisch, Tim O; Wedemeyer, Heiner; Ellis, Ewa C; Ljunggren, Hans-Gustaf; Michaëlsson, Jakob; Björkström, Niklas K
The Journal of immunology (1950), 03/2015, Volume: 194, Issue: 6Journal Article
Although NK cells are considered innate, recent studies in mice revealed the existence of a unique lineage of hepatic CD49a(+)DX5(-) NK cells with adaptive-like features. Development of this NK cell lineage is, in contrast to conventional NK cells, dependent on T-bet but not Eomes. In this study, we describe the identification of a T-bet(+)Eomes(-)CD49a(+) NK cell subset readily detectable in the human liver, but not in afferent or efferent hepatic venous or peripheral blood. Human intrahepatic CD49a(+) NK cells express killer cell Ig-like receptor and NKG2C, indicative of having undergone clonal-like expansion, are CD56(bright), and express low levels of CD16, CD57, and perforin. After stimulation, CD49a(+) NK cells express high levels of inflammatory cytokines but degranulate poorly. CD49a(+) NK cells retain their phenotype after expansion in long-term in vitro cultures. These results demonstrate the presence of a likely human counterpart of mouse intrahepatic NK cells with adaptive-like features.
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