Mice chronically infected with LCMV were treated with PD-1 monotherapy, IL-2 alone, or combination therapy for 2 weeks. LCMV-specific DbGP33+ CD8+ T cells from spleens of each treatment group were sorted for RNA-seq (a–d) and scRNA-seq (e-j). As a control, naive (CD44lo) CD8+ T cells were also sorted for scRNA-seq (e-j). a, MA plots for gene expression of DbGP33+ CD8+ T cells after the indicated treatments. b–d, GSEA of DbGP33+ CD8+ T cells generated by the indicated treatments for effector signature (acute infection) (b), memory signature (acute infection) (c), and exhaustion signature (chronic infection) (d). e, The t-SNE projection of naive CD44lo CD8+ T cells and DbGP33+ CD8+ T cells in 4 treatment groups during chronic infection. Naive and four treatment samples were distributed and overlaid onto the four clusters. f, Numbers of cells in clusters 1, 2, and 3. g, Numbers of cells in cluster 1. Numbers of total DbGP33+ CD8+ T cells per spleen were estimated from geometric mean of Extended Data Fig. 1b (f, g). h, Normalized expression of several representative genes is shown within the 4 clusters i, Co-expression patterns of Tcf7 and Gzmb in cells of each cluster are shown. j, GSEA of DbGP33+ CD8+ T cells generated by the different treatments for effector signature (acute infection) and exhaustion signature (chronic infection). Enrichment score for the signature in four treatment samples are shown as violin plots with horizontal bars of mean. Results were pooled from 2 (a–c) and 1–2 (e–j) experiments with n = 2–18 mice per group in each experiment. ES, enrichment score; Untx, untreated.