Multi-omics Analysis of Human Blood Cells Reveals Unique Features of Age-associated Type2 CD8 Memory T cells

Matsui, H., Cervantes, M., Khalid, M. M., Tomusiak, A., Dwaraka, V., Landgrave-Gomez, J., Ashok Kumaar, P. V., Chen, Q., Lasky- Su, J., Stone, J., Tiwari, R., Kwok, R., Ichikawa, S., Ambrose, B., Riley, R. R., Vega Hormazabal, G., Floro, A., Alexandru, A. C., Smith, R., Schilling, B. C., Kasler, H. G., Verdin, E.

Buck Institute for Research on Aging · biorxiv

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 to 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 naive 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.

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Research summary

The paper claims that age-dependent changes in immune cell populations lead to a Th2-like cytokine response in memory CD8 T cells. This research is relevant as it explores the mechanisms of immune aging, which could contribute to understanding the root causes of age-related diseases and potentially inform strategies for lifespan extension.

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