NDLI: Microchip-Based Single-Cell Imaging Reveals That CD56dimCD57-KIR-NKG2A+ NK Cells Have More Dynamic Migration Associated with Increased Target Cell Conjugation and Probability of Killing Compared to CD56dimCD57-KIR-NKG2A- NK Cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Önfelt, Björn Forslund, Elin Malmberg, Karl-Johan Sohlberg, Ebba Olofsson, Per E. Enqvist, Monika
Description	Author Affiliation: Forslund E ( Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, 171 65 Stockholm, Sweden); Sohlberg E ( Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden); Enqvist M ( Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden); Olofsson PE ( Department of Applied Physics, Science for Life Laboratory, KTH Royal Institute of Technology, 171 65 Stockholm, Sweden); Malmberg KJ ( Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden); Önfelt B ( Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institutet, 171 65 Stockholm, Sweden)
Abstract	NK cells are functionally educated by self-MHC specific receptors, including the inhibitory killer cell Ig-like receptors (KIRs) and the lectin-like CD94/NKG2A heterodimer. Little is known about how NK cell education influences qualitative aspects of cytotoxicity such as migration behavior and efficacy of activation and killing at the single-cell level. In this study, we have compared the behavior of FACS-sorted CD56(dim)CD57(-)KIR(-)NKG2A(+) (NKG2A(+)) and CD56(dim)CD57(-)KIR(-)NKG2A(-) (lacking inhibitory receptors; IR(-)) human NK cells by quantifying migration, cytotoxicity, and contact dynamics using microchip-based live cell imaging. NKG2A(+) NK cells displayed a more dynamic migration behavior and made more contacts with target cells than IR(-) NK cells. NKG2A(+) NK cells also more frequently killed the target cells once a conjugate had been formed. NK cells with serial killing capacity were primarily found among NKG2A(+) NK cells. Conjugates involving IR(-) NK cells were generally more short-lived and IR(-) NK cells did not become activated to the same extent as NKG2A(+) NK cells when in contact with target cells, as evident by their reduced spreading response. In contrast, NKG2A(+) and IR(-) NK cells showed similar dynamics in terms of duration of conjugation periods and NK cell spreading response in conjugates that led to killing. Taken together, these observations suggest that the high killing capacity of NKG2A(+) NK cells is linked to processes regulating events in the recognition phase of NK-target cell contact rather than events after cytotoxicity has been triggered.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Movement Immunology Cytotoxicity, Immunologic Killer Cells, Natural Nk Cell Lectin-like Receptor Subfamily C Antigens, Cd56 Metabolism Antigens, Cd57 Cell Line Flow Cytometry Hek293 Cells Image Processing, Computer-assisted Microchip Analytical Procedures Biosynthesis Receptors, Kir Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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