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

Year: 2026

Type: article

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, 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 towards a Th2-like phenotype drives a pathogenic Th2-like immune population.

Source: Aging Cell

DOI: 10.1111/acel.70393

Institutions: Buck Institute for Research on Aging, Brigham and Women's Hospital, Harvard University

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790

Funders: Hevolution Foundation, Buck Institute for Research on Aging, National Institutes of Health, National Institute on Aging, National Institute of Allergy and Infectious Diseases

Awards: G1163773571, Cellular senescence and Associated Lysosomal Dysfunction in Immune Aging, G5073187195, Training in Basic Research on Aging and Age-Related Disease

OpenAlex ID: W7127038493