hIL-7-hyFc upregulates genes related to the cell cycle and IL-7 signaling pathway. Naive and memory CD8⁺ T cells at days 0 and 7, and after day 21 (post) were isolated with 6 individuals receiving the high-dose of hIL-7-hyFc (60 μg/kg). Gene expression profiles of isolated naive and memory CD8⁺ T cells were analyzed by RNA-seq. (A-B) Heatmap shows DEGs (adjusted P < .05, |log₂ FC| > 1.0) identified from (A) naive and (B) memory CD8⁺ T cells at day 0 vs day 7 and at day 0 and post. (C, D, and G) GSEA of gene sets related to response to IL-7, anergy, senescence, and exhaustion in the transcriptomes of naive and memory CD8⁺ T cells at each time point. Results are shown as normalized enrichment scores. (C) GSEA of a gene set associated with the cellular response to IL-7 obtained from GO BP in naive and memory CD8⁺ T cells. (D) GSEA of genes upregulated in anergic T cells in naive CD8⁺ T cells (left) and senescent cells in memory CD8⁺ T cells (right). (E) Expression of selected genes related to T-cell functions, including inhibitory, costimulatory, and effector molecules in memory CD8⁺ T cells. (F) GSEA using genes related to T-cell exhaustion in memory CD8⁺ T cells. Statistical analyses were calculated with a Wald test. ns, not significant; ∗∗∗∗P < .0001, ∗∗∗P < .001, ∗∗P < .01, ∗P < .05.