Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

The detailed characterization of human γδ T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T...

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Autores principales:	Juan Pablo Cerapio, Marion Perrier, Fréderic Pont, Marie Tosolini, Camille Laurent, Stéphane Bertani, Jean-Jacques Fournie
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	human gammadelta lymphocyte tumor COVID-19 transcriptome Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a27a6d26c87c414198afed4a74702c02
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spelling	oai:doaj.org-article:a27a6d26c87c414198afed4a74702c022021-11-25T19:13:23ZSingle-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease10.3390/v131122121999-4915https://doaj.org/article/a27a6d26c87c414198afed4a74702c022021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2212https://doaj.org/toc/1999-4915The detailed characterization of human γδ T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ T lymphocytes from (<i>n</i> = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein–Barr virus-positive Hodgkin’s lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.Juan Pablo CerapioMarion PerrierFréderic PontMarie TosoliniCamille LaurentStéphane BertaniJean-Jacques FournieMDPI AGarticlehumangammadeltalymphocytetumorCOVID-19transcriptomeMicrobiologyQR1-502ENViruses, Vol 13, Iss 2212, p 2212 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	human gammadelta lymphocyte tumor COVID-19 transcriptome Microbiology QR1-502
spellingShingle	human gammadelta lymphocyte tumor COVID-19 transcriptome Microbiology QR1-502 Juan Pablo Cerapio Marion Perrier Fréderic Pont Marie Tosolini Camille Laurent Stéphane Bertani Jean-Jacques Fournie Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
description	The detailed characterization of human γδ T lymphocyte differentiation at the single-cell transcriptomic (scRNAseq) level in tumors and patients with coronavirus disease 2019 (COVID-19) requires both a reference differentiation trajectory of γδ T cells and a robust mapping method for additional γδ T lymphocytes. Here, we incepted such a method to characterize thousands of γδ T lymphocytes from (<i>n</i> = 95) patients with cancer or adult and pediatric COVID-19 disease. We found that cancer patients with human papillomavirus-positive head and neck squamous cell carcinoma and Epstein–Barr virus-positive Hodgkin’s lymphoma have γδ tumor-infiltrating T lymphocytes that are more prone to recirculate from the tumor and avoid exhaustion. In COVID-19, both TCRVγ9 and TCRVγnon9 subsets of γδ T lymphocytes relocalize from peripheral blood mononuclear cells (PBMC) to the infected lung tissue, where their advanced differentiation, tissue residency, and exhaustion reflect T cell activation. Although severe COVID-19 disease increases both recruitment and exhaustion of γδ T lymphocytes in infected lung lesions but not blood, the anti-IL6R therapy with Tocilizumab promotes γδ T lymphocyte differentiation in patients with COVID-19. PBMC from pediatric patients with acute COVID-19 disease display similar γδ T cell lymphopenia to that seen in adult patients. However, blood γδ T cells from children with the COVID-19-related multisystem inflammatory syndrome are not lymphodepleted, but they are differentiated as in healthy PBMC. These findings suggest that some virus-induced memory γδ T lymphocytes durably persist in the blood of adults and could subsequently infiltrate and recirculate in tumors.
format	article
author	Juan Pablo Cerapio Marion Perrier Fréderic Pont Marie Tosolini Camille Laurent Stéphane Bertani Jean-Jacques Fournie
author_facet	Juan Pablo Cerapio Marion Perrier Fréderic Pont Marie Tosolini Camille Laurent Stéphane Bertani Jean-Jacques Fournie
author_sort	Juan Pablo Cerapio
title	Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
title_short	Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
title_full	Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
title_fullStr	Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
title_full_unstemmed	Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease
title_sort	single-cell rnaseq profiling of human γδ t lymphocytes in virus-related cancers and covid-19 disease
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/a27a6d26c87c414198afed4a74702c02
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Single-Cell RNAseq Profiling of Human γδ T Lymphocytes in Virus-Related Cancers and COVID-19 Disease

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