Fig. 3. The immune and the central nervous systems are both involved in MND.

8–10 week old CD45.2 WT and KI mice were subjected to hematopoietic cell-ablative doses of irradiation and reconstituted with bone marrow cells from congenic CD45.1 or 1.2 WT or KI animals. After 10 months of reconstitution, chimera were analyzed. a, Experimental schematic. b, Average time to latency before falling from an accelerating rotarod (pool of 3 independent experiments, n=21 (WT/WT), =15 (KI/KI), =20 (KI/WT), =25 (WT/KI) individual mice/group; mean +/− SEM). p-value calculated using a one-way repeated measures ANOVA test (***p=0.0003) and Bonferroni’s post-test. (c,d) Twelve months after reconstitution, peripheral blood cells from two mice of the indicated group were pooled and analyzed by mass cytometry. c, t-SNE plots of FlowSOM metaclusters after gating on total CD45^high (top), TCRβ⁺ (middle) and CD8⁺ PD-1⁺ (bottom) cells. d, Frequency of CD8 T cells expressing PD-1 in the blood. e, Frequency of PD-1⁺ CD5^high CD8 T cells from the SC and brain of the indicated chimeric mice 12 months after reconstitution (2 independent experiments, n=5 mice/group; mean +/− SEM). p-value calculated using one-way ANOVA and Dunnett’s post-test (**p=0.0025; ***p=0.0009).