@article{8f9c4a067191489483a92a3a99b55481,
title = "The dynamics of γδ T cell responses in nonhuman primates during SARS-CoV-2 infection",
abstract = "Although most SARS-CoV-2 infections are mild, some patients develop systemic inflammation and progress to acute respiratory distress syndrome (ARDS). However, the cellular mechanisms underlying this spectrum of disease remain unclear. γδT cells are T lymphocyte subsets that have key roles in systemic and mucosal immune responses during infection and inflammation. Here we show that peripheral γδT cells are rapidly activated following aerosol or intra-tracheal/intra-nasal (IT/IN) SARS-CoV-2 infection in nonhuman primates. Our results demonstrate a rapid expansion of Vδ1 γδT cells at day1 that correlate significantly with lung viral loads during the first week of infection. Furthermore, increase in levels of CCR6 and Granzyme B expression in Vδ1 T cells during viral clearance imply a role in innate-like epithelial barrier-protective and cytotoxic functions. Importantly, the early activation and mobilization of circulating HLA-DR+CXCR3+ γδT cells along with significant correlations of Vδ1 T cells with IL-1Ra and SCF levels in bronchoalveolar lavage suggest a novel role for Vδ1 T cells in regulating lung inflammation during aerosol SARS-CoV-2 infection. A deeper understanding of the immunoregulatory functions of MHC-unrestricted Vδ1 T cells in lungs during early SARS-CoV-2 infection is particularly important in the wake of emerging new variants with increased transmissibility and immune evasion potential.",
author = "Fears, {Alyssa C.} and Walker, {Edith M.} and Nicole Chirichella and Nadia Slisarenko and Merino, {Kristen M.} and Nadia Golden and Breanna Picou and Skye Spencer and Russell-Lodrigue, {Kasi E.} and Doyle-Meyers, {Lara A.} and Blair, {Robert V.} and Beddingfield, {Brandon J.} and Maness, {Nicholas J.} and Roy, {Chad J.} and Namita Rout",
note = "Funding Information: We are grateful to all the veterinary personnel, administrators, and laboratory managers who were involved in this work. We thank Drs. Scott Weaver, Kenneth, and Jessica Plante at University of Texas Medical Branch for provision of the SARS-CoV-2 viral stock used for the innoculations in this study. We acknowledge Mary Barnes and Melissa Pattison of the Pathogen Detection and Quantification Core of Tulane National Primate Research Center (TNPRC) for assistance with the multiplex cytokine detection assays and use of the Bioplex-200 instrumentation, and the clinical veterinary staff in the Division of Veterinary Medicine at TNPRC for coordinating the biospecimen collections. Technical assistance of the flow cytometry core facility staff at the TNPRC is greatly appreciated. We thank Angela Birnbaum in the Office of Biosafety for reviewing and optimizing all technical SOPs and overseeing the safety of this study. We are extremely grateful to the funding from NIAID Contract HHSN272201700033I; NIH ORIP Grant P51OD011104; NIAID grants R21AI140840, and R33AI136100; and NIGMS grant P20GM103629. Funding Information: We are grateful to all the veterinary personnel, administrators, and laboratory managers who were involved in this work. We thank Drs. Scott Weaver, Kenneth, and Jessica Plante at University of Texas Medical Branch for provision of the SARS-CoV-2 viral stock used for the innoculations in this study. We acknowledge Mary Barnes and Melissa Pattison of the Pathogen Detection and Quantification Core of Tulane National Primate Research Center (TNPRC) for assistance with the multiplex cytokine detection assays and use of the Bioplex-200 instrumentation, and the clinical veterinary staff in the Division of Veterinary Medicine at TNPRC for coordinating the biospecimen collections. Technical assistance of the flow cytometry core facility staff at the TNPRC is greatly appreciated. We thank Angela Birnbaum in the Office of Biosafety for reviewing and optimizing all technical SOPs and overseeing the safety of this study. We are extremely grateful to the funding from NIAID Contract HHSN272201700033I; NIH ORIP Grant P51OD011104; NIAID grants R21AI140840, and R33AI136100; and NIGMS grant P20GM103629. Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1038/s42003-022-04310-y",
language = "English (US)",
volume = "5",
journal = "Communications Biology",
issn = "2399-3642",
publisher = "Springer Nature",
number = "1",
}