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Phenotypic heterogeneity and recycling capacity of natural killer cells in normal human pregnancy
Authors:C D Gregory  H Lee  I V Scott  P R Golding
Affiliation:1. Oncology Research Laboratory, Derby City Hospital, Uttoxeter Road, Derby, DE3 3NE U.K.;2. Department of Obstetrics, Derby City Hospital, Uttoxeter Road, Derby, DE3 3NE U.K.;1. Department of Gynecology and Obstetrics, Loma Linda Medical Center, Loma Linda, CA, USA;2. Southern California Liver Center, San Diego, CA, USA;1. Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;2. Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA;1. Department of Child, Adolescent and Women''s Health, School of Public Health, Peking University, Beijing, China;2. Department of Maternal and Child Health, National Health and Family Planning Commission of the People''s Republic of China, Beijing, China;3. Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China;1. Upper Airways Research Laboratory, Faculty of Medicine, Ghent University, Ghent, Belgium;2. Immunoregulation Unit, VIB Center for Inflammation Research, Ghent, Belguim;3. Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium;4. Unit for Structural Biology, VIB Center for Inflammation Research, Ghent, Belgium;5. Department of Biochemistry and Microbiology, Ghent University, Ghent, Belgium;6. Laboratory of Virology, Faculty of Veterinary Medicine, Ghent University, Ghent, Belgium;7. Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands;8. Division of ENT Diseases, CLINTEC, Karolinska Institute, Stockholm, Sweden;1. Division of Stem Cell Pathology, Center for Experimental Medicine and Systems Biology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan;2. Department of Life Science Frontiers, Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, 606-8507, Japan;3. AMED-CREST, AMED 1-7-1 Otemachi, Chiyodaku, Tokyo, 100-0004, Japan;4. Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, 606-8501, Japan;5. Medical-risk Avoidance based on iPS Cells Team, RIKEN Center for Advanced Intelligence Project (AIP), Kyoto, 606-8507, Japan;1. KEMRI-Wellcome Trust Research Programme (KWTRP), Centre for Geographic Medical Research - Coast (CGMRC), Kilifi, Kenya;2. Division of Infection and Immunity, University College London, London, UK;3. Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, UK;4. Great Ormond Street Institute of Child Health, University College London, UK
Abstract:Natural killer (NK) cells have the ability to kill a variety of target cell types and the possibility that such cells could mount an effective attack on the developing fetus has not been discounted. The present study extends previous work showing that maternal NK reactivity against K562 target cells (TC) is reduced during pregnancy. Here we demonstrate using cytotoxicity assays at both the population and single cell level that, although depressed in number, maternal NK cells exhibiting the capacity to kill K562 TC are as lytically active in their ability to recycle and destroy multiple TC as NK cells from non-pregnant females. Moreover, two colour immunofluorescence analysis of the NK cell-associated markers Leu-7 and Leu-11b indicates that, in addition to a reduction in the absolute number of TC conjugate-forming cells, pregnant females present in their peripheral blood a larger proportion of TC-binding Leu-7+11- cells. These cells may be lytically immature. Small changes in NK cell profile and activity in maternal peripheral blood may be indicative of much more significant changes at the feto-maternal interface. It is, however, clear that pregnant females retain a population of highly active NK cells, thus minimising the possibility of immunocompromise.
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