title: Spontaneous and natural cytotoxicity receptor-mediated cytotoxicity are effector functions of distinct natural killer subsets in hepatitis C virus-infected chimpanzees.
abstract: In humans, CD16 and CD56 are used to identify functionally distinct natural killer (NK) subsets. Due to ubiquitous CD56 expression, this marker cannot be used to distinguish between NK cell subsets in chimpanzees. Therefore, functional analysis of distinct NK subsets during hepatitis C virus (HCV) infection has never been performed in these animals. In the present study an alternative strategy was used to identify four distinct NK subsets on the basis of the expression of CD16 and CD94. The expression of activating and inhibiting surface receptors showed that these subsets resemble human NK subsets. CD107 expression was used to determine degranulation of the different subsets in naive and HCV-infected chimpanzees. In HCV-infected chimpanzees increased spontaneous cytotoxicity was observed in CD94(high/dim) CD16(pos) and CD94(low) CD16(pos) subsets. By contrast, increased natural cytotoxicity receptor (NCR)- mediated degranulation after NKp30 and NKp44 triggering was demonstrated in the CD94(dim) CD16(neg) subset. Our findings suggest that spontaneous and NCR-mediated cytotoxicity are effector functions of distinct NK subsets in HCV-infected chimpanzees.
authors: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors: B E
authors: BE
authors: Verstrepen
authors: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors: I G
authors: IG
authors: Nieuwenhuis
authors: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors: P
authors: P
authors: Mooij
authors: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors: W M
authors: WM
authors: Bogers
authors: Department of Gastroenterology and Hepatology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors: A
authors: A
authors: Boonstra
authors: Department of Virology, Biomedical Primate Research Centre, Rijswijk, the Netherlands.
authors: G
authors: G
authors: Koopman
mesh_terms: D000818:Animals; D018420:Ape Diseases; D015550:Cell Degranulation / Q000187:drug effects; D019070:Cell Lineage / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology* / Q000473:pathology / Q000821:virology; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000145:classification / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D052118:Lysosomal-Associated Membrane Protein 1 / Q000235:genetics / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000235:genetics / Q000276:immunology; D055629:Natural Cytotoxicity Triggering Receptor 2 / Q000235:genetics / Q000276:immunology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics / Q000276:immunology; D002679:Pan troglodytes; D017452:Receptors, IgG / Q000235:genetics / Q000276:immunology; D000098546:Interleukin-21
chemical_list: D007376:Interleukin-2; D007378:Interleukins; D052118:Lysosomal-Associated Membrane Protein 1; D051920:NK Cell Lectin-Like Receptor Subfamily D; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D017452:Receptors, IgG; D000098546:Interleukin-21
keywords: cytotoxicity; natural killer cells; other animals; viral