Fig. 6: Human Tregs-IL2pa have long-term survival and exert robust suppressive activity in immunodeficient recipient mice. | Nature Communications

Fig. 6: Human Tregs-IL2pa have long-term survival and exert robust suppressive activity in immunodeficient recipient mice.

From: Expression of an interleukin-2 partial agonist enhances regulatory T cell persistence and efficacy in mouse autoimmune models

Fig. 6

A Dynamics of the absolute number of injected human CD45+ cells in 100 µL of blood. Six- to twenty-week-old male and female NSG mice received 2.2 × 106 unsorted, transduced control Tregs (Ctrl Tregs, n = 3) or Tregs-IL2pa (n = 6) with 9% transduced cells in both groups. Cell survival was evaluated in blood samples. On day 35, the number of injected cells in the blood was significantly higher in mice that received Tregs-IL2pa compared to those receiving Ctrl Tregs (p = 0.0238). Schematic created in BioRender49. B Absolute numbers of injected human CD45+ cells in NSG spleen, lungs, and liver. Mice received 2.6 × 106 unsorted transduced Ctrl Tregs (n = 3) or Tregs-IL2pa (n = 4) with 5% transduced cells in both groups. Cell survival was assessed 49 days post-injection in the organs. Schematic created in BioRender49. C Representative dot plots showing the expression of CD25 and Foxp3 in injected cells. D Suppression of cell-mediated xenogeneic graft-versus-host disease (xeno-GVHD). Eight- to twenty-week-old male and female NSG mice received either 12 × 106 CD3+CD25- cells alone (PBMC, n = 5) or combined with 6 × 106 unsorted autologous transduced Ctrl Tregs (n = 5) or Tregs-IL2pa (n = 6), with approximately 70% of transduced cells in each vector. Mouse weights were monitored every two days and are depicted on the left. Schematic created in BioRender49. Statistically significant differences were observed in the weight of mice receiving Tregs-IL2pa compared to those receiving PBMC only (p = 0.0013) and those receiving Ctrl Tregs (p < 0.0001). Survival curves for xeno-GVHD are presented on the right. The survival rate was significantly higher in mice that received Tregs-IL2pa compared to those that received Ctrl Tregs (p = 0.0428). Data are presented as mean ± SEM in panels (A), (B), and (D) and were analyzed using a two-tailed Mann-Whitney test for panels (A) and (B). In panel (D), a Kruskal-Wallis test was used for weight analysis, and a Gehan-Breslow-Wilcoxon test was used for survival curve comparisons. (*p < 0.05; **p < 0.01; ***p < 0.001, ****p < 0.0001).

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