Figure 4.
TPL2 deficiency in radioresistant cells inhibits immune cell recruitment into the CNS and ameliorates EAE pathogenesis. (A) Lethally irradiated WT and Tpl2-KO mice were adoptively transferred with GFP+ WT bone marrow cells, and the generated chimeric mice were subjected to EAE induction by MOG35-55. Graph represents the clinical scores of WT and Tpl2-KO GFP-chimeric mice. (B–F) The WT and Tpl2-KO GFP+ bone marrow–chimeric mice were either not immunized (B) or immunized with MOG35-55 for EAE induction (for 15 d; C–F). Flow cytometry was performed to monitor the frequency of GFP+ cells in the spleen (B), total CNS-infiltrating cells (GFP+; C and D), and CNS-infiltrating (GFP+CD4+; E and F) CD4+ T cells. Data are presented as representative plots (B, C, and E) or summary graphs (D and F). (G and H) Flow cytometric analyses of the frequency (G) and absolute numbers (H) of IFN-γ– and IL-17–producing CD4+ T cells in the CNS (brain and spinal cord) of MOG35-55-immunized WT and Tpl2-KO GFP-chimeric mice (n = 5 mice per group, day 15 after immunization). (I) Flow cytometric analyses to measure the number of GFP+CD4+ cells in the draining lymph nodes of MOG35-55-immunized WT and Tpl2-KO GFP-chimeric mice. (J) QPCR analyses of the relative mRNA expression level of the indicated proinflammatory genes in the spinal cords of MOG35-55-immunized WT and Tpl2-KO GFP-chimeric mice (n = 4 mice per group, day 15 after immunization). Data were normalized to a reference gene, Actb. *, P < 0.05. Data are representative of two independent experiments for all panels. Error bars are mean ± SD values.