Single-cell protein expression profiling resolves circulating and resident memory T cell diversity across tissues and infection contexts

Maximilien Evrard, Etienne Becht, Raissa Fonseca, Andreas Obers, Simone L. Park, Nagela Ghabdan-Zanluqui, Jan Schroeder, Susan N. Christo, Dominik Schienstock, Junyun Lai, Thomas N. Burn, Allison Clatch, Imran G. House, Paul Beavis, Axel Kallies, Florent Ginhoux, Scott N. Mueller, Raphael Gottardo, Evan W. Newell, Laura K. Mackay

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Memory CD8+ T cells can be broadly divided into circulating (TCIRCM) and tissue-resident memory T (TRM) populations. Despite well-defined migratory and transcriptional differences, the phenotypic and functional delineation of TCIRCM and TRM cells, particularly across tissues, remains elusive. Here, we utilized an antibody screening platform and machine learning prediction pipeline (InfinityFlow) to profile >200 proteins in TCIRCM and TRM cells in solid organs and barrier locations. High-dimensional analyses revealed unappreciated heterogeneity within TCIRCM and TRM cell lineages across nine different organs after either local or systemic murine infection models. Additionally, we demonstrated the relative effectiveness of strategies allowing for the selective ablation of TCIRCM or TRM populations across organs and identified CD55, KLRG1, CXCR6, and CD38 as stable markers for characterizing memory T cell function during inflammation. Together, these data and analytical framework provide an in-depth resource for memory T cell classification in both steady-state and inflammatory conditions.

Original languageEnglish
Pages (from-to)1664-1680.e9
JournalImmunity
Volume56
Issue number7
DOIs
Publication statusPublished - 11 Jul 2023
Externally publishedYes

Keywords

  • T cell memory
  • surface protein atlas
  • tissue immunity
  • tissue-resident memory T cells

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