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. Author manuscript; available in PMC: 2019 Oct 1.
Published in final edited form as: Nat Immunol. 2019 Apr 1;20(6):724–735. doi: 10.1038/s41590-019-0346-9

Figure 5: Direct impact of IL-10 and IL-35 signaling on CD8+ TILs.

Figure 5:

a, Experimental schematic of adoptive transfer system to generate an environment in which only CD8+ T cells lack IL-10R or IL-35R.

b, Tumor growth curve of Rag1−/− mice that were sequentially reconstituted with CD8-depleted splenocytes and CD8+ T cells from wild-type (WT) (n=11), IL-10R−/− (Il10rb−/−) (n=8), or IL-35R−/−(CD4Cre.Il6stL/L.Il12rb2 KO) (n=7) mice followed by B16 intradermal inoculation. Each measurement time point represents mean value with s.e.m. error bar. Statistical significance was determined by Two-way ANOVA with Holm-Sidak multiple comparisons (****p<0.0001).

c, Representative flow plots depicting the expression of PD-1 against the other 4 inhibitory receptors (TIM3, LAG3, TIGIT, 2B4) and SPICE plots showing the multi-inhibitory receptor expression on the donor CD8+ T cells infiltrating B16 tumor-bearing reconstituted Rag1−/− mice 18 days post-tumor inoculation as described in (a).

d, Scatter-bar graphs representing the percent distribution of donor CD8+ TILs based on the number of inhibitory receptors expressed. (WT: n=10, IL-10R−/−: n=6, IL-35R−/−: n=7). Bars represent mean values. Statistical significance was determined by One-way ANOVA with Holm-Sidak multiple comparisons (****p<0.0001 and other p-values indicated).

(a-d) Data averaged from 2 independent experiments.