Extended Data Fig. 8: CXCR6-dependent clonal expansion and tissue residency programs in brain CD8⁺ T cells from 5xFAD mice.

a, UMAP and violin plots showing Cxcr6 expression in brain CD8⁺ T cells. b, UMAP of Pdcd1 expression (also shown in Fig. 4e) or Cxcr6 and Pdcd1 coexpression (purple color) in brain CD8⁺ T cell subclusters shown in a. c, UMAP of CD8⁺ T cells from a public dataset of Non-Tg and APP/PS1 mice¹¹ colored by genotypes. d, Expression of Cxcr6, Pdcd1 or their overlap (purple color) on subclusters shown in c. e, CXCR6⁺PD-1⁺CD8⁺ T cells (3 months: Non-Tg (n = 3) and 5xFAD (n = 3); 6 months: Non-Tg (n = 4) and 5xFAD (n = 4); 9 months: Non-Tg (n = 4) and 5xFAD (n = 4); 12 months: Non-Tg (n = 5) and 5xFAD (n = 10)) in the brains of Non-Tg and 5xFAD mice at indicated time points. f, g, Subclustered brain CD8⁺ T cells from indicated mice colored by genotype (f) or subclusters (g). h, UMAP and violin plot of Pdcd1 expression in brain CD8⁺ T cell subclusters in g. i, PD-1⁺CD8⁺ T cells in the brains of APP^NL-G-F;Cxcr6^+/+ (n = 10) and APP^NL-G-F;Cxcr6^–/– (n = 11) mice. j, CD69⁺CXCR6⁺CD8⁺ T cells from 10-month-old Non-Tg (n = 5) and 5xFAD (n = 8) mice. k, l, GSEA enrichment plots showing downregulated core T_RM cell signature in clonally expanded (k) or Pdcd1⁺ brain CD8⁺ T cells (l) from 5xFAD;Cxcr6^–/– versus 5xFAD;Cxcr6^+/+ mice. m, CD69⁺, CD103⁺, and CD69⁺CD103⁺ among brain CD8⁺ T cells from 4-month-old APP^NL-G-F;Cxcr6^+/+ (n = 10) and APP^NL-G-F;Cxcr6^–/– (n = 11) mice. Data were analyzed by two-way ANOVA (e), two-tailed unpaired Student’s t-test (i, j, m), two-tailed normalized weighted Kolmogorov–Smirnov test (NES for k and l), or two-tailed Benjamini–Hochberg adjusted P value (FDR for k and l). Data are shown as mean ± s.e.m. in e, i, j and m; NS, not significant. Data were pooled from at least three (12 months in e, i and j), two (6 and 9 months in e and m) or one (3-month-old mice in e) independent experiments.

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