Memory CD8+ T cell heterogeneity is primarily driven by pathogen-specific cues and additionally shaped by the tissue environment

Esmé T.I. van der Gracht, Guillaume Beyrend, Tamim Abdelaal, Iris N. Pardieck, Thomas H. Wesselink, Floortje J. van Haften, Suzanne van Duikeren, Frits Koning, Ramon Arens

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

SummaryFactors that govern the complex formation of memory T cells are not completelyunderstood. A better understanding of thedevelopment of memory Tcell hetero-geneity is however required to enhance vaccination and immunotherapy ap-proaches. Here we examined the impact of pathogen- and tissue-specific cueson memory CD8+T cell heterogeneity using high-dimensional single-cell mass cy-tometry and a tailored bioinformatics pipeline. We identified distinct populationsof pathogen-specific CD8+T cells that uniquely connected to a specific pathogenor associated to multiple types of acute and persistent infections. In addition, thetissue environment shaped the memory CD8+T cell heterogeneity, albeit to alesser extent than infection. The programming of memory CD8+T cell differenti-ation during acute infection is eventually superseded by persistent infection.Thus, the plethora of distinct memory CD8+T cell subsets that arise upon infec-tion is dominantly sculpted by the pathogen-specific cues and further shaped by the tissue environment.


Original languageEnglish
Article number101954
Number of pages35
JournaliScience
Volume24
Issue number1
DOIs
Publication statusPublished - 2021

Keywords

  • Cell Biology
  • Immunology

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