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Figure 2

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MPTP-induced nigrostriatal pathway injury stimulates T cell brain infiltration in mouse.

(A) Schematic representation of the experimental approach (see Methods). The green circle within reconstituted mice refers to the lymphoid compartments replenished with GFP+ cells. (B) GFP+ T cell infiltration in the SNpc and (C) striatum following MPTP intoxication. Numerous GFP+ T cells can be seen in the SNpc 2 days after MPTP but not saline exposure. GFP+ T cells are also found in the striatum from intoxicated mice, though there are far fewer than in the SNpc. Scale bars: 300 μm (B); 100 μm (C); 10 μm (insets). (D) Immunofluorescent staining for TH, Glut1, CD8, or CD4. Note that infiltrated GFP+ T cells are clustered within the SNpc in close proximity to TH+ DNs. Transmigrated GFP+ T cells are not found in the lumen of Glut1+ blood vessels (arrows) and consist of both CD8+ and CD4+ T cell subsets. Scale bars: 20 μm. (E) T cell brain infiltration in MPTP-treated C57BL/6 inbred mice. CD3 immunostaining showing numerous T lymphocytes within the SNpc (dashed line) from MPTP-treated mice (left panel). Scale bar: 100 μm. Kinetic of nigral CD4+ and CD8+ T cell (insets) density after MPTP exposure (right panel). S, saline. Data points represent the mean ± SEM. *P < 0.01 compared with saline- and MPTP-treated mice at day 4 after MPTP exposure; P < 0.01 compared with saline-treated controls (Tukey post-hoc analysis). Scale bars: 50 μm. (F) Double immunofluorescence staining for PCNA and GFP and GFAP or Mac1. Note that PCNA+ cells in the SNpc never colocalize with GFP+ or GFAP+ cells, whereas they superpose perfectly with Mac-1+ macrophages/microglial cells (arrows). Scale bar: 50 μm.

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