Multi-omics Analysis of Human Blood Cells Reveals Unique Features of Age-associated Type2 CD8 Memory T cells
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.
Authors
- Birgit Schilling (ORCID: https://orcid.org/0000-0001-9907-2749)
- Benjamin D Ambrose
- Hiroyuki Matsui
- Eric Verdin (ORCID: https://orcid.org/0000-0003-3703-3183)
- Rebeccah Riley (ORCID: https://orcid.org/0000-0002-5870-6837)
- Ritesh Tiwari
- Alan Tomusiak (ORCID: https://orcid.org/0000-0002-1522-5339)
- Marlene Cervantes
- Qingwen Jia Xiaohan Chen
- Ariel Floro (ORCID: https://orcid.org/0009-0004-7460-8059)
- Mir M. Khalid (ORCID: https://orcid.org/0000-0002-1862-6795)
- Herbert G. Kasler (ORCID: https://orcid.org/0000-0002-6660-4267)
- Varun B. Dwaraka (ORCID: https://orcid.org/0000-0001-9033-3092)
- J. H. Stone
- Jorge Landgrave-Gómez
- Ryan Kwok (ORCID: https://orcid.org/0000-0002-1850-6611)
- Genesis Vega Hormazabal
- Prasanna Vadhana Ashok Kumaar
- Andreea Cristina Alexandru (ORCID: https://orcid.org/0000-0002-9300-6246)
- Ryan Smith
- Jesica Lasky-Su
- Shuntaro Ichikawa
Institutions
- Brigham and Women's Hospital (US)
- Buck Institute for Research on Aging (US)
- Harvard University (US)
- VPDiagnostics (United States) (US)
Publication Details
- Journal
- bioRxiv (Cold Spring Harbor Laboratory)
- Published
- 2025-12-26
- DOI
- https://doi.org/10.64898/2025.12.23.696247
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Buck Institute for Research on Aging