The cell-surface 5'-nucleotidase CD73 defines a functional T memory cell subset that declines with age

Area of Science:

• Immunology
• Cell Biology
• Aging Research

Background:

• Immune memory is crucial for protective immunity but declines with age.
• T cell heterogeneity contributes to immune memory function.
• Age-associated immune dysfunction (immunosenescence) impairs protective responses.

Purpose of the Study:

• To investigate the role of T cell heterogeneity in age-associated immune memory failure.
• To identify novel T cell subsets associated with aging and immune memory.
• To characterize the function and regulation of age-associated T cell subsets.

Main Methods:

• Screening for age-dependent T cell-surface markers in CD4 and CD8 memory T cells.
• Functional characterization of identified T cell subsets.
• Analysis of chromatin accessibility and transcriptomes.
• Investigation of upstream regulatory factors, including transcription factors.

Main Results:

• Identified novel CD4 and CD8 memory T cell subsets distinct from central and effector memory cells.
• Discovered that memory T cells expressing CD73 (ecto-5'-nucleotidase) decline with age.
• These CD73+ memory T cells are polyfunctional, poised for effector functions, and can differentiate into tissue-resident memory T cells (TRMs).
• Transcription factors regulating chromatin accessibility and transcriptomes were identified as facilitators of CD73 expression and TRM differentiation.

Conclusions:

• Age-associated decline in CD73+ memory T cells contributes to impaired immune memory.
• CD73+ memory T cells represent a critical subset with long-lived, polyfunctional, and tissue-homing potential.
• CD73 is directly involved in T cell survival and is regulated by specific transcription factors, offering potential therapeutic targets.