title: Cutting edge: identification and characterization of human intrahepatic CD49a+ NK cells.
abstract: 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.
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Nicole
authors: N
authors: Marquardt
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Vivien
authors: V
authors: Béziat
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Sanna
authors: S
authors: Nyström
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors: Julia
authors: J
authors: Hengst
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Martin A
authors: MA
authors: Ivarsson
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Eliisa
authors: E
authors: Kekäläinen
authors: Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and.
authors: Helene
authors: H
authors: Johansson
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Jenny
authors: J
authors: Mjösberg
authors: Center for Fetal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden.
authors: Magnus
authors: M
authors: Westgren
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors: Tim O
authors: TO
authors: Lankisch
authors: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors: Heiner
authors: H
authors: Wedemeyer
authors: Division of Transplantation Surgery, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; and.
authors: Ewa C
authors: EC
authors: Ellis
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Hans-Gustaf
authors: HG
authors: Ljunggren
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden;
authors: Jakob
authors: J
authors: Michaëlsson
authors: Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden; niklas.bjorkstrom@ki.se.
authors: Niklas K
authors: http://orcid.org/0000-0002-0967-076X
authors: NK
authors: Björkström
mesh_terms: D000328:Adult; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D039423:Integrin alpha1 / Q000276:immunology* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000276:immunology / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D054340:Receptors, KIR / Q000276:immunology / Q000378:metabolism
chemical_list: D019002:CD56 Antigen; D016207:Cytokines; D018836:Inflammation Mediators; D039423:Integrin alpha1; C496212:KIR2DS1 protein, human; C527059:KLRC2 protein, human; D055654:NK Cell Lectin-Like Receptor Subfamily C; D017452:Receptors, IgG; D054340:Receptors, KIR