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.
Show 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 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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