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

Maximilien Evrard1, Etienne Becht2, Raissa Fonseca1

  • 1Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Parkville, VIC 3010, Australia.

Immunity
|July 1, 2023
PubMed

Insights

This study reveals new protein markers to distinguish circulating (TCIRCM) and tissue-resident memory T (TRM) cells. These findings offer a deeper understanding of immune cell heterogeneity in various organs during inflammation.

Area of Science:

  • Immunology
  • Cell Biology
  • Systems Biology

Background:

  • Memory CD8+ T cells are crucial for adaptive immunity, comprising circulating (TCIRCM) and tissue-resident (TRM) subsets.
  • Phenotypic and functional differences between TCIRCM and TRM cells across diverse tissues are not fully understood.

Purpose of the Study:

  • To comprehensively profile proteins in TCIRCM and TRM cells across multiple organs.
  • To identify stable markers for characterizing memory T cell populations in steady-state and inflammatory conditions.

Main Methods:

  • Utilized an antibody screening platform and machine learning pipeline (InfinityFlow) to analyze >200 proteins.
  • Profiled TCIRCM and TRM cells from nine organs in murine models of local and systemic infection.
  • Evaluated strategies for selective ablation of TCIRCM or TRM populations.

Main Results:

  • Discovered significant heterogeneity within TCIRCM and TRM cell lineages across different organs.
  • Identified CD55, KLRG1, CXCR6, and CD38 as stable markers for memory T cell characterization.
  • Demonstrated effective strategies for selectively targeting TCIRCM or TRM populations.

Conclusions:

  • The study provides an in-depth resource for classifying memory T cells.
  • The findings enhance our understanding of immune cell diversity and function in health and disease.