Extended Data Fig. 8: Phenotypes of age-dependent accumulative T cells in hippocampus with advancing age.

a, UMAP plot of immune population in the current dataset. b, Pie chart of the proportion of T cells detected in all three ages (young: 6.5%; middle-age: 27.6%; old: 65.9%). c, T cells in old brains express Cd8 and phenotypes of effector memory (Cd62L⁻Cd44⁺), tissue retention (Itgal⁺Itga4⁺) and activation (Cd69⁺Xcl1⁺). d, Violin plots showing upregulated expression of IFN-γ and Pdcd1 in T cells at the advancing ages. e, Representative images showing the emergency of T cells in the white matter of old brains (upper: corpus callosum; lower: fimbria) (n = 10 mice). f-g, Representative images showing parenchyma-residential status (non-vessel-associated) (f) and local amplification (Ki67⁺) (g) of T cells in old hippocampi (n = 10 mice). h, Representative images showing the majority of T cells in the non-DG hippocampal subregions of old brains were CD8⁺. i, Pie chart of the proportion of CD8⁺ T cells in all CD3⁺ T cells of the old mouse brain (CD8⁺CD3⁺ T cells: 82.3%; CD8⁻CD3⁺ T cells: 17.7%; n = 10 mice). j, Representative images showing the inflammatory and cytotoxic phenotypres of CD8⁺ T cells in the old mouse non-DG jippocampus (n = 4 mice). k, Feature plots of NK cell-specific gene (Ncr1), CD8⁺ T cell-specific gene (Cd8a) and cytotoxicity-related gene (Gzmb). Color gradient indicates the log-normalized gene expression level. l, Representative images of GZMB⁺CD8⁻ cells in the old DG (n = 4 mice). GCL, granule cell layer, ML, molecular layer, NK, natural killer, SLM, stratum lacunosum moleculare, SO, stratum oriens, SP, stratum pyramidale and SR, stratum radiatum. All data were presented as mean ± SEM. Scale bars, (a-b) 100 μm (20 μm zoom-in panels), (d) 200 μm and (h-i) 20 μm (5 μm zoom-in panels).