Single-cell gene expression and TCR profiling reveal age-related differences in recent thymic emigrants

Area of Science:

• Immunology
• Developmental Biology
• T cell biology

Background:

• CD8+ T cells mature after leaving the thymus, transitioning from recent thymic emigrants (RTEs) to naive T cells.
• RTEs possess distinct phenotypes and functions compared to mature naive T cells.
• Most research on RTEs focuses on adults, leaving a knowledge gap regarding early-life RTEs, which are more abundant.

Purpose of the Study:

• To compare the phenotypes and functions of neonatal and adult CD8+ RTEs.
• To investigate how the T cell receptor (TCR) repertoire influences RTE heterogeneity during development.

Main Methods:

• Utilized a fate mapping mouse model to study CD8+ RTEs.
• Employed paired single-cell transcriptomics and T cell receptor (TCR) sequencing.

Main Results:

• Neonatal and adult CD8+ RTEs exhibit distinct phenotypes and functions.
• Neonatal RTEs display a more effector-like gene expression profile compared to adult RTEs.
• TCR usage significantly impacts the effector-gene bias in both neonatal and adult RTEs, particularly in neonatal germline-encoded TCRs.

Conclusions:

• The composition and characteristics of the RTE pool change significantly during development.
• TCR usage is a key factor contributing to the phenotypic diversity observed within neonatal and adult RTE populations.