title: Natural killer cell subsets and receptor expression in peripheral blood mononuclear cells of a healthy Korean population: Reference range, influence of age and sex, and correlation between NK cell receptors and cytotoxicity.
abstract: BACKGROUND
  The purpose of this study was to identify CD56brightand CD56dimnatural killer (NK) cell subsets and analyze their receptors expression in a healthy Korean population, and to determine whether receptor expression correlates with age, sex, and cytotoxicity.
  
  
  METHODS
  We performed multicolor flow cytometry assays to analyze the expression of various NK cell receptors (CD16, NKG2A, NKG2C, NKG2D, CD57, DNAM-1, CD8a, CD62L, NKp30, and NKp46) on both CD3-/CD56dimand CD3-/CD56brightNK cells in whole-blood samples from 122 healthy donors. The expression of these receptors was compared according to age (<30years, n=22, 30-60years, n=73 and >60years, n=27) and gender (male, n=61, female, n=61). NK cell cytotoxicity assays were performed with peripheral blood mononuclear cells (PBMCs) from 18 individuals. The results were compared to the expression levels of NKp30 and NKp46 receptors.
  
  
  RESULTS
  A normal reference range for NK cell receptor expression in two NK cell subsets was established. NKp46 and NKG2D expression gradually decreased with age (p<0.01 and p<0.05, respectively) whereas NK cell proportion and numbers, frequencies of CD56dimcells, and CD57 expression increased with age (p<0.01 in all cases). Men showed greater NK cell proportion and numbers, frequencies of CD56dimcells, and CD57 expression compared to those of women (p<0.05 and p<0.001; p<0.01 and p<0.01, respectively). Notably, the expression of NKp46 was negatively correlated with NK cell frequency (r=-0.42, p<0.001). Furthermore, NK cell cytotoxicity was found to positively correlate with NCR expression (p=0.02), but not NK cell proportion (p=0.80).
  
  
  CONCLUSIONS
  We have established a profile of NK cell surface receptors for a Korean population, and revealed that age and gender have an effect on the expression of NK cell receptors in the population. Our data might explain why neither NK cell numbers nor proportions correlate with NK cell cytotoxicity.
authors.affiliation: Center for Creative Biomedical Scientists, Chonnam National University, GwangJu, South Korea; Department of Laboratory Medicine, Chonnam National University, GwangJu, South Korea.
authors.forename: Minh-Trang
authors.initials: MT
authors.lastname: Phan
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, South Korea.
authors.forename: Sejong
authors.initials: S
authors.lastname: Chun
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, South Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Alaa Kassim
authors.initials: AK
authors.lastname: Ali
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Canada.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Immunotherapy Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine, Chonnam National University, GwangJu, South Korea. Electronic address: alpinboy@chonnam.ac.kr.
authors.forename: Soo-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, South Korea; Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, South Korea. Electronic address: duck.cho@skku.edu.
authors.forename: Duck
authors.initials: D
authors.lastname: Cho
mesh_terms: D000328:Adult; D000368:Aged; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D019002:CD56 Antigen / Q000276:immunology / Q000378:metabolism*; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007723:Korea; D008297:Male; D008875:Middle Aged; D055607:Receptors, Natural Killer Cell / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D019002:CD56 Antigen; D055607:Receptors, Natural Killer Cell
keywords: Cytotoxicity; NCR; NK cells; Receptor; Reference range; Subset