Fig. 5: Detrimental CD103–CD8+ Trm cells in the brain originate from the circulation and their depletion ameliorates disease in 3xTg-AD mice. | Nature Communications

Fig. 5: Detrimental CD103–CD8+ Trm cells in the brain originate from the circulation and their depletion ameliorates disease in 3xTg-AD mice.

From: CD103–CD8+ T cells promote neurotoxic inflammation in Alzheimer’s disease via granzyme K–PAR-1 signaling

Fig. 5

a Flow cytometry showing the percentage of brain CD103– and CD103+CD8+ Trm cells after anti-CD8 antibody treatment. Anti-CD8 (WT, n = 6; 3xTg-AD, n = 9), isotype-control (WT, n = 6; 3xTg-AD, n = 9). Data are means ± SD from two independent experiments and P-values are based on one-way ANOVA-multiple comparisons was used. b Time spent during training (MWM test). Anti-CD8 (WT, n = 10; 3xTg-AD, n = 21), isotype-control (WT, n = 22; 3xTg-AD, n = 18). Data are means ± SD from two-independent experiments (two-way ANOVA-multiple comparisons). c Representative tracking of three mice/group (MWM test). d, e Violin plots showing path efficiency (d) and number of body rotations (e) (MWM test). Data are from two-independent experiments one-way ANOVA-multiple comparisons). f Bar plot showing the percentage of freezing during the CFC test after anti-CD8 treatment. Anti-CD8 (WT, n = 9; 3xTg-AD, n = 16), isotype-control (WT, n = 21; 3xTg-AD, n = 13). Data are means ± SD from two-independent experiments. One-way ANOVA-multiple comparisons was used. g–i Immunohistochemical staining of the hippocampus after CD8 T cell depletion showing Aβ-load (g), the levels of hyperphosphorylated (h) and total (i) tau protein. Anti-CD8 (n = 3), isotype-control (n = 3). Scale bar = 20 µm. Data are means ± SEM. Two-tailed Student’s t-test was used. ROI = 624.7 µm×501.22 µm. j–l ELISA showing Aβ 1−40 and Aβ 1−42 (j) levels of tau hyperphosphorylation (k) and total tau (l) in soluble and insoluble fractions of brain homogenates after anti-CD8 treatment. Anti-CD8 (n = 4), isotype control (n = 4). Data from three-independent experiments are means ± SEM (two-tailed Student’s t-test). m Dot blot showing insoluble oligomeric and fibrillar forms of Aβ in brain homogenates after anti-CD8 treatment. Anti-CD8 (n = 4), isotype-control (n = 4). Data from three-independent experiments are shown as means ± SEM. P-values based on two-tailed Student’s t-test. n Immunofluorescence staining showing hippocampal oligomeric and fibrillar Aβ. Scale bar = 10 µm.

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