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 (Leiden University Medical Center)
Guillaume Beyrend (Leiden University Medical Center)
Tamim Abdelaal (TU Delft - Electrical Engineering, Mathematics and Computer Science, Leiden University Medical Center)
Iris N. Pardieck (Leiden University Medical Center)
Thomas H. Wesselink (Leiden University Medical Center)
Floortje J. van Haften (Leiden University Medical Center)
Suzanne van Duikeren (Leiden University Medical Center)
Frits Koning (Leiden University Medical Center)
Ramon Arens (Leiden University Medical Center)
More Info
expand_more
Other than for strictly personal use, it is not permitted to download, forward or distribute the text or part of it, without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license such as Creative Commons.
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 The programming of memory CD8+T cell differenti-ation during acute infection is eventually superseded by persistent infection.Thus, the plethora of distinct memory CD8+T cell subsets that arise upon infec-tion is dominantly sculpted by the pathogen-specific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.
help_outline