Aging induces T cells with distinct transcriptomic profiles and functions in brain-associated tissues

Area of Science:

• Immunology
• Neuroscience
• Aging Research

Background:

• Aging impacts lymphocyte populations, altering their molecular and functional traits.
• The aging effects on CD4+ and CD8+ T cell transcriptomes in non-lymphoid tissues, like the brain, are not well understood.
• Studying transcriptomic changes in aging tissue-infiltrating immune cells offers insights into tissue homeostasis and age-related diseases.

Purpose of the Study:

• To investigate the impact of aging on the transcriptome and function of CD4+ and CD8+ T cells within brain-associated tissues.
• To identify specific T cell subsets that change during aging in the brain.
• To explore the functional significance of aging-associated T cells in the brain.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) to compare T cell subsets and transcriptomes in young and aged mouse meninges and choroid plexus.
• Flow cytometry to analyze aging-associated CD4+ T cells in the hippocampus.
• Antibody-mediated depletion to assess the functional role of aging-associated T cells.

Main Results:

• Aging shifts CD4+ and CD8+ T cell transcriptomes in the meninges and choroid plexus towards an effector memory phenotype.
• Aged mice exhibit increased T helper 2 (Th2) cells, regulatory T cells (Tregs), and CD153-expressing CD4+ T cells in brain-associated regions.
• CD153-expressing CD4+ T cells were found in the hippocampus, and their depletion impaired cognitive function.

Conclusions:

• Aging significantly alters the transcriptome of brain-associated CD4+ and CD8+ T cells.
• Accumulation of specific CD153-expressing CD4+ T cells in the meninges, choroid plexus, and hippocampus is a hallmark of aging.
• These CD153+ T cells may play a crucial protective role in maintaining brain homeostasis during aging.