Transcriptomic analysis of human IL‐7 receptor alpha low and high effector memory CD8+ T cells reveals an age‐associated signature linked to influenza vaccine response in older adults

Here, we investigated the relationship of the age‐associated expansion of IL‐7 receptor alpha low (IL‐7Rαlow) effector memory (EM) CD8+ T cells with the global transcriptomic profile of peripheral blood cells in humans. We found 231 aging signature genes of IL‐7Rαlow EM CD8+ T cells that corresponded to 15% of the age‐associated genes (231/1,497) reported by a meta‐analysis study on human peripheral whole blood from approximately 15,000 individuals, having high correlation with chronological age. These aging signature genes were the target genes of several transcription factors including MYC, SATB1, and BATF, which also belonged to the 231 genes, supporting the upstream regulatory role of these transcription factors in altering the gene expression profile of peripheral blood cells with aging. We validated the differential expression of these transcription factors between IL‐7Rαlow and high EM CD8+ T cells as well as in peripheral blood mononuclear cells (PBMCs) of young and older adults. Finally, we found a significant association with influenza vaccine responses in older adults, suggesting the possible biological significance of the aging signature genes of IL‐7Rαlow EM CD8+ T cells. The results of our study support the relationship of the expansion of IL‐7Rαlow EM CD8+ T cells with the age‐associated changes in the gene expression profile of peripheral blood cells and its possible biological implications. Human effector memory (EM) CD8+ T cells expressing low levels of IL‐7 receptor alpha chain (IL‐7Rα), which expand with aging, have a unique set of genes (e.g. GZMH, FGFBP2, CX3CR1) that correlate with chronological age. These genes referred to as the aging signature genes of IL‐7Rα EM CD8+ T cells are targeted largely by the transcription factors MYC, SATB1 and BATF, and associated with influenza vaccine responses in older adults.