PMID- 30857329
OWN - NLM
STAT- MEDLINE
DCOM- 20190918
LR  - 20200309
IS  - 1999-4915 (Electronic)
IS  - 1999-4915 (Linking)
VI  - 11
IP  - 3
DP  - 2019 Mar 9
TI  - Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2C(null) Human 
      Immunodeficiency Virus-Infected Individuals.
LID - 10.3390/v11030239 [doi]
LID - 239
AB  - Expansion of natural killer (NK) cells expressing NKG2C occurs following human 
      cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus 
      (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced 
      CD16-dependent cytokine production and downregulate FcepsilonRIgamma and promyelocytic 
      leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV 
      infection, but whether this affects NK cell acquisition of superior 
      antibody-dependent function is unclear. Therefore, our objective was to 
      investigate whether HCMV-driven NK cell differentiation is impaired in 
      NKG2C(null) HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcepsilonRIgamma, 
      and PLZF expression) and functional (cytokine induction and cytotoxicity) 
      properties were compared between HIV(-)infected NKG2C(null) and NKG2C-expressing 
      groups. Cytokine production was compared following stimulation through natural 
      cytotoxicity receptors or through CD16. Cytotoxicity was measured by 
      anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated 
      cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) 
      antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell 
      differentiation in HIV infection with or without NKG2C. While the fraction of 
      mature (CD57(pos)) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and 
      CD16 (p = 0.03) was significantly higher in NKG2C(null) HIV-infected individuals, 
      there were no significant differences in NKG2A, FcepsilonRIgamma, or PLZF expression. The 
      general phenotypic and functional equivalency observed suggests NKG2C-independent 
      routes of HCMV-driven NK cell differentiation, which may involve increased CD2 
      expression.
FAU - Comeau, Emilie M
AU  - Comeau EM
AD  - Immunology and Infectious Diseases Program, Division of BioMedical Sciences, 
      Faculty of Medicine, Memorial University of Newfoundland, 300 Prince Philp Drive, 
      St. John's, NL A1B 3V6, Canada. emc878@mun.ca.
FAU - Holder, Kayla A
AU  - Holder KA
FAU - Fudge, Neva J
AU  - Fudge NJ
FAU - Grant, Michael D
AU  - Grant MD
LA  - eng
GR  - PJT 361426/CIHR/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190309
PL  - Switzerland
TA  - Viruses
JT  - Viruses
JID - 101509722
RN  - 0 (Cytokines)
RN  - 0 (FCGR3B protein, human)
RN  - 0 (FcepsilonRI gamma-chain, human)
RN  - 0 (GPI-Linked Proteins)
RN  - 0 (KLRC2 protein, human)
RN  - 0 (NK Cell Lectin-Like Receptor Subfamily C)
RN  - 0 (Promyelocytic Leukemia Zinc Finger Protein)
RN  - 0 (Receptors, IgE)
RN  - 0 (Receptors, IgG)
RN  - 147855-37-6 (ZBTB16 protein, human)
SB  - IM
MH  - Adult
MH  - Antibody-Dependent Cell Cytotoxicity
MH  - Cell Differentiation
MH  - Coinfection/immunology/virology
MH  - Cytokines/immunology
MH  - Cytomegalovirus/*pathogenicity
MH  - Cytomegalovirus Infections/*immunology
MH  - Female
MH  - GPI-Linked Proteins/genetics/immunology
MH  - HIV Infections/*immunology
MH  - Humans
MH  - Killer Cells, Natural/cytology/*virology
MH  - Lymphocyte Activation
MH  - Male
MH  - Middle Aged
MH  - NK Cell Lectin-Like Receptor Subfamily C/*genetics/immunology
MH  - Promyelocytic Leukemia Zinc Finger Protein/genetics/immunology
MH  - Receptors, IgE/genetics/immunology
MH  - Receptors, IgG/genetics/immunology
PMC - PMC6466323
OTO - NOTNLM
OT  - ADCC
OT  - CD16
OT  - CD2
OT  - FcepsilonRIgamma
OT  - HCMV
OT  - HIV
OT  - NKG2A
OT  - NKG2C
OT  - NKG2Cnull
OT  - PLZF
COIS- The authors declare no conflict of interest.
EDAT- 2019/03/13 06:00
MHDA- 2019/09/19 06:00
PMCR- 2019/03/01
CRDT- 2019/03/13 06:00
PHST- 2019/02/11 00:00 [received]
PHST- 2019/03/01 00:00 [revised]
PHST- 2019/03/05 00:00 [accepted]
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2019/09/19 06:00 [medline]
PHST- 2019/03/01 00:00 [pmc-release]
AID - v11030239 [pii]
AID - viruses-11-00239 [pii]
AID - 10.3390/v11030239 [doi]
PST - epublish
SO  - Viruses. 2019 Mar 9;11(3):239. doi: 10.3390/v11030239.