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

Hiroyuki Matsui, Marlene Cervantes, Mir M Khalid, Alan Tomusiak, Varun Dwaraka, Jorge Landgrave-Gomez, Prasanna Vadhana Ashok Kumaar, Qingwen Chen, Jessica Lasky-Su, Jake Stone, Ritesh Tiwari, Ryan Kwok, Shuntaro Ichikawa, Benjamin D Ambrose, Rebeccah R Riley, Genesis Vega Hormazabal, Ariel Adkisson-Floro, Andreea Cristina Alexandru, Ryan Smith, Birgit Schilling, Herbert G Kasler, Eric Verdin

Buck Institute for Research on Aging, Novato, California, USA.Buck Institute for Research on Aging, Novato, California, USA. · pubmed

Paper

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.

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Research summary

The paper claims that an age-dependent drift in epigenetic regulation leads to a pathogenic Th2-like immune population in aging individuals. This research is relevant as it explores the underlying mechanisms of immune aging, which could contribute to understanding and potentially mitigating age-related diseases.

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