Figure 4.
Non–T-cell-derived IL-10 production promotes loss of immune control after SCT. Recipients were transplanted as previously described with BM+T grafts from B6 donors. (A) MM-bearing recipients of WT (blue) or IL-10–deficient (IL-10−/−; red) grafts were monitored for survival and bled to quantify tumor burden using M-band (G/A). M-bands were modeled over time to calculate a predictive rate of tumor growth (indicated by solid line), with confidence intervals shaded and M-band relapse threshold shown as dotted line (n = 9-10 combined from 2 experiments). (B) Frequency of TIM-3 and PD-1 expression on CD8+ T cells from BM of MM-bearing recipients transplanted with grafts from CD4cre+ × IL-10Rfl/fl (red) or Cre-negative littermate control (blue) donors. FACS plots are representative. BM was harvested from MM-relapsed mice at 6 to 7 weeks after transplant (n = 7 combined from 2 experiments). (C-D) Survival of MM-bearing recipients transplanted with BM+T from (C) CD4cre+ × IL-10Rfl/fl (red) or Cre-negative littermate control (blue) donors (n = 10-11 combined from 2 experiments) and (D) CD4cre+ × IL-10fl/fl (red) or Cre-negative littermate control or WT (blue) donors (n = 15 combined from 2 experiments). (E-H) Recipients were transplanted with grafts from FoxP3-RFP × IL-10-GFP reporter donors. WT donors (Reporterneg) were used to define the IL-10+ gating strategy. Recipients were sacrificed 8 weeks after transplant, BM and spleen were harvested, and cells were analyzed using flow cytometry. (E) Representative FACS plots in BM. (F) Spearman r correlation of frequency of IL-10+ cells with MM burden in BM and spleen of MM-bearing mice (n = 32 combined from 4 experiments). (G-H) Total number of IL-10+ cells (G) and number of CD3+ and CD3− IL-10–producing cells (H) in the BM and spleen of MM-relapsed, MM-controlled, and MM-free mice (n = 16-17 combined from 4 experiments). To determine statistical significance, tumor burden was plotted using longitudinal mixed-effects linear models, and survival was analyzed using a log-rank test. A Mann-Whitney U test was used for numerical values and data are presented as mean ± SEM. *P < .05, **P < .01, ***P < .001.

Non–T-cell-derived IL-10 production promotes loss of immune control after SCT. Recipients were transplanted as previously described with BM+T grafts from B6 donors. (A) MM-bearing recipients of WT (blue) or IL-10–deficient (IL-10−/−; red) grafts were monitored for survival and bled to quantify tumor burden using M-band (G/A). M-bands were modeled over time to calculate a predictive rate of tumor growth (indicated by solid line), with confidence intervals shaded and M-band relapse threshold shown as dotted line (n = 9-10 combined from 2 experiments). (B) Frequency of TIM-3 and PD-1 expression on CD8+ T cells from BM of MM-bearing recipients transplanted with grafts from CD4cre+ × IL-10Rfl/fl (red) or Cre-negative littermate control (blue) donors. FACS plots are representative. BM was harvested from MM-relapsed mice at 6 to 7 weeks after transplant (n = 7 combined from 2 experiments). (C-D) Survival of MM-bearing recipients transplanted with BM+T from (C) CD4cre+ × IL-10Rfl/fl (red) or Cre-negative littermate control (blue) donors (n = 10-11 combined from 2 experiments) and (D) CD4cre+ × IL-10fl/fl (red) or Cre-negative littermate control or WT (blue) donors (n = 15 combined from 2 experiments). (E-H) Recipients were transplanted with grafts from FoxP3-RFP × IL-10-GFP reporter donors. WT donors (Reporterneg) were used to define the IL-10+ gating strategy. Recipients were sacrificed 8 weeks after transplant, BM and spleen were harvested, and cells were analyzed using flow cytometry. (E) Representative FACS plots in BM. (F) Spearman r correlation of frequency of IL-10+ cells with MM burden in BM and spleen of MM-bearing mice (n = 32 combined from 4 experiments). (G-H) Total number of IL-10+ cells (G) and number of CD3+ and CD3− IL-10–producing cells (H) in the BM and spleen of MM-relapsed, MM-controlled, and MM-free mice (n = 16-17 combined from 4 experiments). To determine statistical significance, tumor burden was plotted using longitudinal mixed-effects linear models, and survival was analyzed using a log-rank test. A Mann-Whitney U test was used for numerical values and data are presented as mean ± SEM. *P < .05, **P < .01, ***P < .001.

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