# Multi‐Omics Analysis of Human Blood Cells Reveals Unique Features of Age‐Associated Type 2 CD8 Memory T Cells

## TL;DR

This study finds that aging leads to a specific type of immune cell that contributes to diseases like asthma and diabetes.

## Contribution

The study identifies a novel age-related CD8 T cell population with Th2-like features linked to disease.

## Key findings

- Aging increases CXCR3- central memory CD8 T cells with Th2-like cytokine responses.
- These cells are associated with asthma, chronic liver conditions, and type 2 diabetes.
- Epigenetic changes support a Th2-like immune profile in aged individuals.

## Abstract

Aging impacts immune function, but the mechanisms driving age‐related changes in immune cell subsets remain unclear. To explore age‐dependent changes in immune cell populations, we analyzed human peripheral blood mononuclear cells (PBMCs) from a cohort of healthy donors aged 20–82 years using a 36‐color spectral flow cytometry panel focused on T cells. We identified a unique population of memory CD8 T cells, which lack CXCR3 and produce a Th2‐like cytokine response, and accumulate with age. We discovered an age‐dependent bias in naïve CD8 T cells toward Th2 cytokine production, accompanied by transcriptional and epigenetic changes supporting this phenotype. Moreover, health outcome association analysis linked the accumulation of these unique CXCR3‐ central memory CD8 T cells to asthma, chronic liver conditions, and type 2 diabetes. Together, our results support the model that an age‐dependent drift in epigenetic regulation toward a Th2‐like phenotype drives a pathogenic Th2‐like immune population.

Aging drives the accumulation of CXCR3‐ central memory CD8 T cells that exhibit Th2‐like transcriptional and epigenetic programs. These cells display a pathogenic Th2‐skewed profile and are associated with age‐related diseases, including asthma, chronic liver disease, and type 2 diabetes.