Extended Data Fig. 10: Blocking PD-1 immune checkpoint increases Foxp3⁺CD4⁺ Tregs and reduces tau-mediated neurodegeneration.

(a) The gating strategy for sorting Foxp3⁺ CD4⁺ Treg, Pd1⁺ Foxp3⁺ CD4⁺ Treg, Klrg1⁺ effector CD8⁺ T cells, PD-1⁺ Tox1⁺ CD8⁺ exhausted T cells in the brain parenchyma. (b–e) Quantification of T cell populations in the brain parenchyma of mice acutely treated with IgG control and αPD-1 antibodies. (TE4-IgG: n = 12 and TE4-αPD-1: n = 13 for b, d, e; TE4-IgG: n = 10 and TE4-αPD-1: n = 11 for c). *p = 0.041, **p = 0.0075, p = 0.52, p = 0.945 for Foxp3⁺CD4⁺ Treg, Pd1⁺ Foxp3⁺ CD4⁺ Treg, Klrg1⁺ effector CD8⁺ T cells, PD-1⁺ Tox1⁺ CD8⁺ exhausted T cells. Unpaired two-tailed Student’s t test. (f) Representative images of 9.5-month TE4-IgG and TE4-αPD-1 treated mouse brain sections stained with Sudan black. Scale bar = 1 mm. (g-h) Volumes of hippocampus, entorhinal/piriform cortex in 9.5-month TE4-IgG and TE4-αPD-1 treated mice. (TE4-IgG: n = 14 and TE4-αPD-1: n = 14). *p = 0.018 and 0.015 for TE4-IgG vs. TE4-αPD-1 in comparing the volumes of hippocampus, entorhinal/piriform cortex, respectively. Unpaired two-tailed Student’s t test. (i) Quantification of the area covered by AT8 in DG per slice in 9.5-month TE4-IgG vs. TE4-αPD-1 mice (TE4-IgG: n = 14 and TE4-αPD: n = 14). **p = 0.0009. Unpaired two-tailed Student’s t test.