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

ABSTRACT

We investigated the effect of aging on the multi-dimensional characteristics and heterogeneity of human peripheral CD8+ T cells defined by the expression of a set of molecules at the single cell level using the recently developed mass cytometry or Cytometry by Time-Of-Flight (CyTOF) and computational algorithms. CD8+ T cells of young and older adults had differential expression of molecules, especially those related to cell activation and migration, permitting the clustering of young and older adults through an unbiased approach. The changes in the expression of individual molecules were collectively reflected in the altered high-dimensional profiles of CD8+ T cells in older adults as visualized by the dimensionality reduction analysis tools principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE). A combination of PhenoGraph clustering and t-SNE analysis revealed heterogeneous subsets of CD8+ T cells that altered with aging. Furthermore, intermolecular quantitative relationships in CD8+ T cells appeared to change with age as determined by the computational algorithm conditional-Density Resampled Estimate of Mutual Information (DREMI). The results of our study showed that heterogeneity, multidimensional characteristics, and intermolecular quantitative relationships in human CD8+ T cells altered with age, distinctively clustering young and older adults through an unbiased approach.