Extended Data Fig. 4: CXCR6 promotes brain CD8+ T cell accumulation.
From: CXCR6 orchestrates brain CD8+ T cell residency and limits mouse Alzheimer’s disease pathology
a, Widefield immunofluorescence images of CD3+ T cells, Aβ and Iba1+ microglia in brains of indicated 10-month-old mice. Scale bar, 200 μm. White arrows indicate positive staining for CD3+ T cells. Boxed areas show CD3 staining insets. b, CD4+ and CD8+ T cells in the meninges (upper left, 5xFAD;Cxcr6+/+ (n = 13) and 5xFAD;Cxcr6–/– (n = 9)), spleen (upper right, 5xFAD;Cxcr6+/+ (n = 16) and 5xFAD;Cxcr6–/– (n = 17)), liver (lower left, 5xFAD;Cxcr6+/+ (n = 8) and 5xFAD;Cxcr6–/– (n = 10)), or lung (lower right, 5xFAD;Cxcr6+/+ (n = 7) and 5xFAD;Cxcr6–/– (n = 10)) of indicated 10-month-old mice. c–f, Indicated immune cell populations in the brains of 10-month-old female and male 5xFAD;Cxcr6+/+ (c, d; n = 10, 10, 6, 6, 10, and 6 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in female mice, respectively; and 12, 12, 9, 9, 9, and 7 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in male mice, respectively) and 5xFAD;Cxcr6–/– mice (c, d; n = 14, 14, 7, 7, 13 and 7 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in female mice, respectively; and 13, 13, 11, 11, 11, and 7 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg in male mice, respectively), or in 4-month-old APPNL-G-F;Cxcr6+/+ (e, f; n = 5, 5, 5, 5, 4 and 5 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in female mice, respectively; and 5, 5, 5, 5, 5, and 5 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in male mice, respectively) and APPNL-G-F;Cxcr6–/– (e, f; n = 5, 5, 5, 5, 4 and 5 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in female mice, respectively; and 6, 6, 6, 6, 6, and 6 for CD8+ T cells, CD4+ T cells, NK1.1 cells, NKT cells, γδ T cells, and eTreg cells in male mice, respectively) mice. g, Non-viable (Zombie Aqua+) CD8+ T cells in indicated tissues of 10-month-old 5xFAD;Cxcr6+/+ (n = 13, 9, 9, 4 for meninges, spleen, liver, lung, respectively) and 5xFAD;Cxcr6–/– (n = 9, 12, 12, 7 for meninges, spleen, liver, lung, respectively) mice. h, Ki67+ cells among brain CD8+ T cells from 10-month-old 5xFAD;Cxcr6+/+ (n = 8) and 5xFAD;Cxcr6–/– (n = 9) mice. Data were analyzed by two-tailed unpaired Student’s t-test (b–h). Data are shown as mean ± s.e.m. in b–h; NS, not significant. Data were pooled from at least two (b–h) independent experiments or are representative of two (a) independent experiments.
