Figure 7.

XBP-1s inhibition reduces pathogenic Th17 and Th1 cells, yet preserves generation of anti-tumor CTL and Tregs in vivo. NSG mice were transplanted with human skin grafts and allogeneic PBMCs and treated with vehicle or B-I09 exactly as described. On day +21, the mouse spleens were harvested and human T cell phenotypes were determined by flow cytometry. The amount of human (A,B) Th17s (CD4⁺, IL-17A⁺), (C,D) Tregs (CD4⁺, CD127⁻, CD25⁺, Foxp3⁺), Th1s (CD4⁺ IFNγ⁺), and Th2s (CD4⁺, IL-4⁺) (E–G) isolated from the recipient spleen at day +21 are shown. Pooled data from two independent experiments, up to 7 mice per group, Mann-Whitney test. (H) Replicate mean specific lysis by human CD8⁺ CTL generated in vivo using NSG mice transplanted with human PBMCs (30 × 10⁶) and vaccinated with irradiated U937cells (10 × 10⁶) on days 0 and +7. Mice received B-I09 or vehicle as described. For these experiments, recipients did not receive human skin. U937 lysis was measured by a colorimetric assay after 4 h using purified human CD8⁺ T cells from recipient spleens at days +10–12. Replicate mean tumor lysis values shown are from 1 of 2 independent experiments, Tukey's test.