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

Area of Science:

• Immunology
• Cell Biology
• Systems Biology

Background:

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

Purpose of the Study:

• To comprehensively profile proteins in T_CIRCM and T_RM 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 T_CIRCM and T_RM cells from nine organs in murine models of local and systemic infection.
• Evaluated strategies for selective ablation of T_CIRCM or T_RM populations.

Main Results:

• Discovered significant heterogeneity within T_CIRCM and T_RM 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 T_CIRCM or T_RM 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.