Increased Chemokine Production is a Hallmark of Rhesus Macaque Natural Killer Cells Mediating Robust Anti-HIV Envelope-Specific Antibody-Dependent Cell-Mediated Cytotoxicity

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Published: Jan 23, 2025
Keywords:
Rhesus Macaque, NK cells, Antibody-Dependent Cell Cytotoxicity, Single-Cell Gene Expression Analysis, Chemokine

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Junsuke Nohara
Department of Molecular Genetics and Microbiology, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine, Durham, NC
Tyler Evangelous
Human Vaccine Institute, Duke University School of Medicine, Durham, NC
Madison Berry
Human Vaccine Institute, Duke University School of Medicine, Durham, NC
Whitney Beck
Human Vaccine Institute, Duke University School of Medicine, Durham, NC
Sarah Mudrak
Human Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine, Durham, NC
Shalini Jha
Department of Surgery, Duke University School of Medicine, Durham, NC
R. Keith Reeves
Department of Surgery, Duke University School of Medicine; Duke Research and Discovery at RTP, Duke University Health System; Center for Human Systems Immunology, Duke University; Department of Pathology, Duke University School of Medicine, Durham, NC
Kevin J. Wiehe
Human Vaccine Institute, Duke University School of Medicine, Durham, NC
Justin Pollara
Human Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NC
Georgia D. Tomaras
Department of Molecular Genetics and Microbiology, Duke University School of Medicine; Human Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NC
Todd Bradley
Genomic Medicine Center, Children’s Mercy Research Institute, Children’s Mercy Kansas City; Departments of Pediatrics and Pathology and Laboratory Medicine, University of Kansas Medical Center; Department of Pediatrics, UMKC School of Medicine, Kansas City, MO
Guido Ferrari
Human Vaccine Institute, Duke University School of Medicine; Department of Surgery, Duke University School of Medicine; Center for Human Systems Immunology, Duke University, Durham, NC
https://orcid.org/0000-0001-7747-3349

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.

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Vol. 10 No. 1 (2024): Volume 10, Number 1
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