Identification of the predominant human NK cell effector subset mediating ADCC against HIV-infected targets coated with BNAbs or plasma from PLWH.


Journal

European journal of immunology
ISSN: 1521-4141
Titre abrégé: Eur J Immunol
Pays: Germany
ID NLM: 1273201

Informations de publication

Date de publication:
08 2021
Historique:
revised: 12 04 2021
received: 21 01 2021
accepted: 02 06 2021
pubmed: 5 6 2021
medline: 8 10 2021
entrez: 4 6 2021
Statut: ppublish

Résumé

The potential of immunotherapy strategies utilizing broadly neutralizing antibodies (BNAbs), such as 3BNC117 and 10-1074, to limit viral replication while also facilitating clearance of HIV infected cells has heightened interest in identifying the predominant NK effector subset(s) capable of mediating antibody dependent cellular cytotoxicity (ADCC). Utilizing advanced polychromatic flow cytometry, we identified that CD57 positive NK cells from ART-suppressed in People Living With HIV (PLWH) expressed significantly higher levels of the CD16 FcγR receptor, 2B4 ADCC coreceptor, and HLA-DR activation marker while NKG2C positive NK cells expressed significantly higher levels of the CD2 ADCC coreceptor (p < 0.001, n = 32). Functionally, CD57 positive NK cells from ART-suppressed PLWH with either high or low NKG2C expansion exhibited significantly enhanced degranulation and IFN-γ production against heterologous gp120-coated ADCC targets coated with HIV reference plasma compared to CD57 negative NK cells (p = 0.0029, n = 11). CD57 positive NK cells from control donors lacking NKG2C expansion also exhibited significantly more degranulation and IFN-γ production at every timepoint tested against both heterologous ADCC targets (p = 0.019, n = 9) and HIV-1 infected autologous CD4

Identifiants

pubmed: 34086344
doi: 10.1002/eji.202149188
pmc: PMC8338900
mid: NIHMS1711165
doi:

Substances chimiques

Broadly Neutralizing Antibodies 0
HIV Antibodies 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2051-2061

Subventions

Organisme : NIAID NIH HHS
ID : UM1 AI126620
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI136756
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA040554
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA049666
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI120828
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA048728
Pays : United States
Organisme : NIAID NIH HHS
ID : R56 AI120828
Pays : United States

Informations de copyright

© 2021 Wiley-VCH GmbH.

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Auteurs

Costin Tomescu (C)

HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.

Kyle Kroll (K)

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Krystal Colon (K)

HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.

Emmanouil Papasavvas (E)

HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.

Ian Frank (I)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Pablo Tebas (P)

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Karam Mounzer (K)

Jonathan Lax Center, Philadelphia FIGHT, Philadelphia, PA, USA.

Roger Keith Reeves (RK)

Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ragon Institute of Massachusetts General Hospital, MIT, and Harvard, Cambridge, MA, USA.

Luis J Montaner (LJ)

HIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, PA, USA.

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Classifications MeSH