Quantifiable blood TCR repertoire components associate with immune aging

Area of Science:

• Immunology
• Computational Biology
• Gerontology

Background:

• T cell senescence impairs adaptive immunity in aging individuals.
• The dynamic changes in T cell clones with aging remain poorly understood.
• Existing research has not established a clear link between aging and T cell clone alterations.

Purpose of the Study:

• To investigate age-associated changes in T cell receptor (TCR) repertoires.
• To identify and characterize dynamic T cell clone changes linked to aging.
• To explore the potential of these changes as biomarkers for immune function and clinical outcomes.

Main Methods:

• Development and application of a novel computational framework, Repertoire Functional Units (RFU).
• Analysis of over 6500 publicly available TCR repertoire sequencing samples from diverse human cohorts.
• Quantification of RFU reduction with aging and under immunosuppressive conditions.
• Systematic analysis of age-associated RFUs in clinical samples.

Main Results:

• Identification of consistent age-associated RFUs across multiple human cohorts.
• Demonstration of accelerated RFU reduction with aging, particularly under immunosuppression.
• Association of specific age-associated RFUs with improved clinical outcomes in acute viral infections (e.g., lower ICU admission).
• Observation of secondary expansion of age-associated clones post-bone marrow transplantation from younger donors.

Conclusions:

• The study suggests the existence of a 'TCR clock' reflecting immune function in aging populations.
• Age-associated RFUs may serve as indicators of immune status and clinical prognosis.
• Understanding T cell clone dynamics with aging is crucial for immune health in older individuals.