Figure 4.

Functional T cells are developed in CCST and BLT mice

(A) Pre-B leukemic REH cells expressing luciferase were injected in the three humanized models, and mice were imaged weekly by injecting D-luciferin to follow the progression of the leukemic cells. Depicted are representative BLT, CCST, and humNSG mice with different capabilities to respond to the REH challenge.

(B) Intensity of the luciferase expression (expressed in photons per cm²) was used as a surrogate marker of leukemia progression in BLT mice (red line), CCST mice (blue line), and humNSG mice (green line). Medians ± range are shown for the luciferase signal. p = 0.0111 between BLT and CCST, p = 0.0002 between humNSG and CCST, and p < 0.0001 between BLT and humNSG (two-way ANOVA).

(C) Survival curves show a significant difference (log-rank tests) between BLT (n = 10, red line), CCST (n = 14, blue line), and humNSG (n = 8, green line). BLT versus humNSG: p < 0.0001; BLT versus CCST: p = 0.0135; CCST versus humNSG: p = 0.0001.

(D) Proliferative capacity of peripheral blood T cells isolated from the three models of humanized mice was tested by ex vivo stimulation with 5 μg/mL PHA-L for 24 h in the presence of EdU. Representative flow-cytometry plots are shown for each model.

(E) Enumeration of hCD4⁺hCD8⁺EdU⁺ cells showed that T cells from CCST (n = 7) and BLT (n = 8) mice proliferated significantly more than humNSG (n = 7) mice (p = 0.0061 with CCST, p < 0.0001 with BLT). T cells isolated from CCST mice proliferated also less than BLT (p = 0.0466). One-way ANOVA with Tukey’s post hoc test.

^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001, ^∗∗∗∗p < 0.0001.