Dissecting alterations in human CD8+ T cells with aging by high-dimensional single cell mass cytometry

Area of Science:

• Immunology
• Cell Biology
• Computational Biology

Background:

• Aging significantly impacts immune system function, leading to increased susceptibility to infections and reduced vaccine efficacy.
• CD8+ T cells play a crucial role in adaptive immunity, and their functional decline with age is a key hallmark of immunosenescence.

Purpose of the Study:

• To investigate the multi-dimensional characteristics and heterogeneity of human peripheral CD8+ T cells in young versus older adults.
• To identify age-associated changes in molecular expression, cellular subsets, and intermolecular relationships within CD8+ T cells.

Main Methods:

• Utilized mass cytometry (Cytometry by Time-Of-Flight, CyTOF) for high-dimensional single-cell analysis of CD8+ T cells.
• Applied computational algorithms including PhenoGraph clustering, principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), and conditional-Density Resampled Estimate of Mutual Information (DREMI).

Main Results:

• Significant differences in molecular expression, particularly for activation and migration markers, were observed between young and older adults.
• Unbiased clustering revealed distinct CD8+ T cell populations that varied with age, visualized through PCA and t-SNE.
• Aging altered intermolecular quantitative relationships within CD8+ T cells, as identified by DREMI analysis.

Conclusions:

• Human peripheral CD8+ T cell heterogeneity and multi-dimensional characteristics are significantly altered with age.
• Age-dependent changes in CD8+ T cells create distinct profiles that allow for unbiased clustering of young and older individuals.
• These findings provide novel insights into the immunobiology of aging at the single-cell level.