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Transcriptome Analysis of Single Cells
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Single-cell transcriptome analysis of CD8 + T-cell memory inflation.

Andrew J Highton1, Madeleine E Zinser1, Lian Ni Lee1

  • 1Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford, Oxfordshire, OX13SY, UK.

Wellcome Open Research
|August 27, 2019
PubMed
Summary

Persistent viruses and vaccines create unique CD8+ T-cell memory, known as memory inflation. This study maps the distinct gene expression differentiating spleen and gut T-cell memory, crucial for mucosal immunity.

Keywords:
adenovirus vectorcytomegalovirusmemory T cellsmemory inflationresident-memory T cells

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Area of Science:

  • Immunology
  • Virology
  • Transcriptomics

Background:

  • Persistent viruses like murine cytomegalovirus (MCMV) and adenovirus vaccines induce sustained CD8+ T-cell responses termed memory inflation.
  • These memory T-cells maintain functionality, migrate to peripheral organs, and exhibit a unique transcriptional profile.

Purpose of the Study:

  • To elucidate the transcriptional mechanisms underlying CD8+ T-cell memory inflation at different anatomical sites.
  • To compare virus-specific T-cell populations in the spleen and gut intra-epithelial lymphocytes (IEL) of MCMV-infected mice.

Main Methods:

  • Utilized single-cell RNA sequencing on tetramer-sorted cells from MCMV-infected mice.
  • Analyzed transcriptional networks within virus-specific CD8+ T-cell populations from the spleen and gut IEL.

Main Results:

  • Generated a comprehensive transcriptional map of T-cell memory.
  • Identified a distinct gene expression module differentiating splenic memory inflation from gut resident memory T-cells (T_RM).

Conclusions:

  • CD8+ T-cell memory in the gut epithelium exhibits a unique quality compared to conventional and inflationary memory.
  • These findings may hold significance for developing strategies to enhance protection against mucosal infections.