Extended Data Fig. 11: IL-2(V) is biologically active in vivo but PD-1 + IL-2v combination therapy preferentially expands non-LCMV-specific PD-1 negative CD8+ T cells.
From: PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program
a, Experimental setup for b–c. Mice chronically infected with LCMV were left untreated, or treated with IL-2(WT) or IL-2(V) (modified IL-2 with abolished CD25 binding) for 2 weeks. Expansion of CD8+ T cells was examined in the spleen and blood in the three groups of mice. b, Numbers of CD8+ T cells. c, Numbers of CD44+ CD8+ T cells. d, Experimental setup for panels e–g. Chronically infected mice were untreated, or treated with anti-PD-L1 antibody, anti-PD-L1 plus IL-2(WT), or anti-PD-L1 plus IL-2(V) for 2 weeks. Expansion of PD-1 negative and PD-1 positive CD8+ T cells was examined in the spleen and blood in the four groups of mice. e, Representative FACS plots for CD44 and PD-1 expression on CD8+ T cells in the spleen and blood after the various treatments. f, Numbers of CD44+ PD-1 negative CD8+ T cells in the spleen and blood. g, Numbers of CD44+ PD-1 positive CD8+ T cells in the spleen and blood (per 1×106 PBMCs) of the four groups. Results were pooled from 3 experiments with at least 6 mice per group. Data are presented as geometric mean and 95% CI (b, c, f, g) with p values. Red box highlights preferential expansion of PD-1 negative CD8+ T cells by combination therapy with anti-PD-L1 and IL-2(V) whereas combination therapy with anti-PD-L1 and IL-2(WT) expands PD-1 positive CD8+ T cells. Statistical comparisons were performed using Kruskal-Wallis test with Dunn’s multiple-comparison test. Untx, untreated.
