PMID- 24154599
OWN - NLM
STAT- MEDLINE
DCOM- 20140620
LR  - 20240323
IS  - 1946-6242 (Electronic)
IS  - 1946-6234 (Print)
IS  - 1946-6234 (Linking)
VI  - 5
IP  - 208
DP  - 2013 Oct 23
TI  - Genetic and environmental determinants of human NK cell diversity revealed by 
      mass cytometry.
PG  - 208ra145
LID - 10.1126/scitranslmed.3006702 [doi]
AB  - Natural killer (NK) cells play critical roles in immune defense and reproduction, 
      yet remain the most poorly understood major lymphocyte population. Because their 
      activation is controlled by a variety of combinatorially expressed activating and 
      inhibitory receptors, NK cell diversity and function are closely linked. To 
      provide an unprecedented understanding of NK cell repertoire diversity, we used 
      mass cytometry to simultaneously analyze 37 parameters, including 28 NK cell 
      receptors, on peripheral blood NK cells from 5 sets of monozygotic twins and 12 
      unrelated donors of defined human leukocyte antigen (HLA) and killer cell 
      immunoglobulin-like receptor (KIR) genotype. This analysis revealed a remarkable 
      degree of NK cell diversity, with an estimated 6000 to 30,000 phenotypic 
      populations within an individual and >100,000 phenotypes in the donor panel. 
      Genetics largely determined inhibitory receptor expression, whereas activation 
      receptor expression was heavily environmentally influenced. Therefore, NK cells 
      may maintain self-tolerance through strictly regulated expression of inhibitory 
      receptors while using adaptable expression patterns of activating and 
      costimulatory receptors to respond to pathogens and tumors. These findings 
      further suggest the possibility that discrete NK cell subpopulations could be 
      harnessed for immunotherapeutic strategies in the settings of infection, 
      reproduction, and transplantation.
FAU - Horowitz, Amir
AU  - Horowitz A
AD  - Department of Structural Biology, Stanford University School of Medicine, 
      Stanford, CA 94305, USA.
FAU - Strauss-Albee, Dara M
AU  - Strauss-Albee DM
FAU - Leipold, Michael
AU  - Leipold M
FAU - Kubo, Jessica
AU  - Kubo J
FAU - Nemat-Gorgani, Neda
AU  - Nemat-Gorgani N
FAU - Dogan, Ozge C
AU  - Dogan OC
FAU - Dekker, Cornelia L
AU  - Dekker CL
FAU - Mackey, Sally
AU  - Mackey S
FAU - Maecker, Holden
AU  - Maecker H
FAU - Swan, Gary E
AU  - Swan GE
FAU - Davis, Mark M
AU  - Davis MM
FAU - Norman, Paul J
AU  - Norman PJ
FAU - Guethlein, Lisbeth A
AU  - Guethlein LA
FAU - Desai, Manisha
AU  - Desai M
FAU - Parham, Peter
AU  - Parham P
FAU - Blish, Catherine A
AU  - Blish CA
LA  - eng
GR  - T32 AI007290/AI/NIAID NIH HHS/United States
GR  - T32 AI07290/AI/NIAID NIH HHS/United States
GR  - AI057229/AI/NIAID NIH HHS/United States
GR  - AI22039/AI/NIAID NIH HHS/United States
GR  - U19AI090019/AI/NIAID NIH HHS/United States
GR  - R01 AI022039/AI/NIAID NIH HHS/United States
GR  - UL1 RR025744/RR/NCRR NIH HHS/United States
GR  - UL1 TR001085/TR/NCATS NIH HHS/United States
GR  - DA011170/DA/NIDA NIH HHS/United States
GR  - ES022153/ES/NIEHS NIH HHS/United States
GR  - U19 AI057229/AI/NIAID NIH HHS/United States
GR  - R01 DA023063/DA/NIDA NIH HHS/United States
GR  - R01 DA011170/DA/NIDA NIH HHS/United States
GR  - AI07290/AI/NIAID NIH HHS/United States
GR  - R21 ES022153/ES/NIEHS NIH HHS/United States
GR  - U19 AI090019/AI/NIAID NIH HHS/United States
GR  - P01 CA111412/CA/NCI NIH HHS/United States
GR  - P30 AI027757/AI/NIAID NIH HHS/United States
GR  - AI090019/AI/NIAID NIH HHS/United States
GR  - DA023063/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Sci Transl Med
JT  - Science translational medicine
JID - 101505086
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Receptors, Natural Killer Cell)
SB  - IM
CIN - Nat Rev Immunol. 2013 Dec;13(12):844-5. PMID: 24189575
CIN - Nat Biotechnol. 2014 Feb;32(2):140-2. PMID: 24509762
CIN - Nat Rev Immunol. 2019 Feb;19(2):69. PMID: 30626905
MH  - Adult
MH  - Cluster Analysis
MH  - *Environment
MH  - Female
MH  - Gene Expression Regulation
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Immunologic Memory
MH  - Killer Cells, Natural/*cytology/*metabolism
MH  - Male
MH  - Mass Spectrometry/*methods
MH  - Middle Aged
MH  - Phenotype
MH  - Receptors, Natural Killer Cell/*genetics
MH  - Young Adult
PMC - PMC3918221
MID - NIHMS536454
EDAT- 2013/10/25 06:00
MHDA- 2014/06/21 06:00
PMCR- 2014/10/23
CRDT- 2013/10/25 06:00
PHST- 2013/10/25 06:00 [entrez]
PHST- 2013/10/25 06:00 [pubmed]
PHST- 2014/06/21 06:00 [medline]
PHST- 2014/10/23 00:00 [pmc-release]
AID - 5/208/208ra145 [pii]
AID - 10.1126/scitranslmed.3006702 [doi]
PST - ppublish
SO  - Sci Transl Med. 2013 Oct 23;5(208):208ra145. doi: 10.1126/scitranslmed.3006702.