Deep profiling deconstructs features associated with memory CD8+ T cell tissue residence

Milcah Scott, Zoë Steier, Mark J. Pierson, J. Michael Stolley, Stephen D. O’Flanagan, Andrew G. Soerens, Sathi P. Wijeyesinghe, Lalit K. Beura, Gayathri Dileepan, Brandon J. Burbach, Marco Künzli, Clare F. Quarnstrom, Olivia C. Ghirardelli Smith, Eyob Weyu, Sara E. Hamilton, Vaiva Vezys, Alex K. Shalek, david masopust

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue-resident memory CD8+ T (Trm) cells control infections and cancer and are defined by their lack of recirculation. Because migration is difficult to assess, residence is usually inferred by putative residence-defining phenotypic and gene signature proxies. We assessed the validity and universality of residence proxies by integrating mouse parabiosis, multi-organ sampling, intravascular staining, acute and chronic infection models, dirty mice, and single-cell multi-omics. We report that memory T cells integrate a constellation of inputs—location, stimulation history, antigen persistence, and environment—resulting in myriad differentiation states. Thus, current Trm-defining methodologies have implicit limitations, and a universal residence-specific signature may not exist. However, we define genes and phenotypes that more robustly correlate with tissue residence across the broad range of conditions that we tested. This study reveals broad adaptability of T cells to diverse stimulatory and environmental inputs and provides practical recommendations for evaluating Trm cells.

Original languageEnglish (US)
Pages (from-to)162-181.e10
JournalImmunity
Volume58
Issue number1
DOIs
StatePublished - Jan 14 2025

Bibliographical note

Publisher Copyright:
© 2024

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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