Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved]
Background: Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8+ T-cell responses, described as memory “inflation”. These retain functionality, home to peripheral organs and are associated with a distinct transcriptional program. Method...
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doaj-bec4a62e35804da0864da57582d498ea2020-11-25T00:40:41ZengWellcomeWellcome Open Research2398-502X2019-05-01410.12688/wellcomeopenres.15115.116491Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved]Andrew J. Highton0Madeleine E. Zinser1Lian Ni Lee2Claire L. Hutchings3Catherine De Lara4Chansavath Phetsouphanh5Chris B. Willberg6Claire L. Gordon7Paul Klenerman8Emanuele Marchi9Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKNational Institute for Health Research Oxford Biomedical Research Centre, Oxford, OX42PG, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKPeter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UKBackground: Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8+ T-cell responses, described as memory “inflation”. These retain functionality, home to peripheral organs and are associated with a distinct transcriptional program. Methods: To further define the nature of the transcriptional mechanisms underpinning memory inflation at different sites we used single-cell RNA sequencing of tetramer-sorted cells from MCMV-infected mice, analyzing transcriptional networks in virus-specific populations in the spleen and gut intra-epithelial lymphocytes (IEL). Results: We provide a transcriptional map of T-cell memory and define a module of gene expression, which distinguishes memory inflation in spleen from resident memory T-cells (TRM) in the gut. Conclusions: These data indicate that CD8+ T-cell memory in the gut epithelium induced by persistent viruses and vaccines has a distinct quality from both conventional memory and “inflationary” memory which may be relevant to protection against mucosal infections.https://wellcomeopenresearch.org/articles/4-78/v1 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Andrew J. Highton Madeleine E. Zinser Lian Ni Lee Claire L. Hutchings Catherine De Lara Chansavath Phetsouphanh Chris B. Willberg Claire L. Gordon Paul Klenerman Emanuele Marchi |
spellingShingle |
Andrew J. Highton Madeleine E. Zinser Lian Ni Lee Claire L. Hutchings Catherine De Lara Chansavath Phetsouphanh Chris B. Willberg Claire L. Gordon Paul Klenerman Emanuele Marchi Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] Wellcome Open Research |
author_facet |
Andrew J. Highton Madeleine E. Zinser Lian Ni Lee Claire L. Hutchings Catherine De Lara Chansavath Phetsouphanh Chris B. Willberg Claire L. Gordon Paul Klenerman Emanuele Marchi |
author_sort |
Andrew J. Highton |
title |
Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] |
title_short |
Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] |
title_full |
Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] |
title_fullStr |
Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] |
title_full_unstemmed |
Single-cell transcriptome analysis of CD8+ T-cell memory inflation [version 1; peer review: 2 approved] |
title_sort |
single-cell transcriptome analysis of cd8+ t-cell memory inflation [version 1; peer review: 2 approved] |
publisher |
Wellcome |
series |
Wellcome Open Research |
issn |
2398-502X |
publishDate |
2019-05-01 |
description |
Background: Persistent viruses such as murine cytomegalovirus (MCMV) and adenovirus-based vaccines induce strong, sustained CD8+ T-cell responses, described as memory “inflation”. These retain functionality, home to peripheral organs and are associated with a distinct transcriptional program. Methods: To further define the nature of the transcriptional mechanisms underpinning memory inflation at different sites we used single-cell RNA sequencing of tetramer-sorted cells from MCMV-infected mice, analyzing transcriptional networks in virus-specific populations in the spleen and gut intra-epithelial lymphocytes (IEL). Results: We provide a transcriptional map of T-cell memory and define a module of gene expression, which distinguishes memory inflation in spleen from resident memory T-cells (TRM) in the gut. Conclusions: These data indicate that CD8+ T-cell memory in the gut epithelium induced by persistent viruses and vaccines has a distinct quality from both conventional memory and “inflationary” memory which may be relevant to protection against mucosal infections. |
url |
https://wellcomeopenresearch.org/articles/4-78/v1 |
work_keys_str_mv |
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