Document Type

Article

Publication Date

1-23-2024

Identifier

DOI: 10.20411/pai.v10i1.734; PMCID: PMC11792536

Abstract

BACKGROUND: Antibody-dependent cell-mediated cytotoxic (ADCC) response mediated by natural killer (NK) cells correlates with decreased infection risk in studies involving simian immunodeficiency virus (SIV)/simian-human immunodeficiency virus (SHIV), and human immunodeficiency virus (HIV) vaccine candidates. Currently, the heterogeneities of the functional subset of rhesus macaque natural killer (RMNK) cells are under-characterized.

METHOD: We engaged the RMNK cells with ADCC-mediating anti-HIV-1 monoclonal antibodies (ADCCAbs) or anti-CD16 antibodies and used CD107a expression as the surrogate marker for RMNK cells actively involved in ADCC. CD107a+ and CD107a- populations were analyzed individually using single-cell RNA sequencing.

RESULTS: Subsets of CD107a+ RMNK cells produced more chemokines than the others, suggesting that these cells not only eliminate infected cells but also provide immunoregulatory signals and potentially curb HIV-1 replication. Crosslinking of Fc gamma receptor IIIa via anti-CD16 antibodies resulted in a significantly higher percentage of degranulating cells than via ADCCAbs. However, the magnitude of degranulation and chemokine production was reduced by 6- to 30-fold.

CONCLUSION: The quality and quantity of receptor engagement are important determinants of achieving an optimal level of the RMNK response.

Journal Title

Pathog Immun

Volume

10

Issue

1

First Page

49

Last Page

79

PubMed ID

39911143

Keywords

Antibody-Dependent Cell Cytotoxicity; Chemokine; NK cells; Rhesus Macaque; Single-Cell Gene Expression Analysis

Comments

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Publisher's Link: https://doi.org/10.20411/pai.v10i1.734

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