1. Non–viral Ag–specific CTLs dampen inflammation in a mouse model of viral meningitis.
Non–viral Ag–specific CTLs dampen inflammation in a mouse model of viral meningitis. (A) Mice were inoculated intracerebrally with LCMV. One group (black line) had been infected with LCMV intraperitoneally 1 month before intracerebral infection and mounted a memory response, and mice were thereby protected. Mice receiving intracerebral LCMV without previous induced memory succumbed to the infection 7.25 days (median) after inoculation (red line). In cell transfer experiments similar to the HI and LO scenarios in the T1D models, 1 × 103 or 1 × 106 non–LCMV-specific OT-I CD8+ T cells were transferred and activated in vivo through peptide immunization. High amounts of OT-I led to a significant delay (P = , 1 × 103 OT-I versus 1 × 106 OT-I, log-rank test) in time to death (n = 6 mice per group; data are representative of two independent experiments). Brains from the mice were examined 7 days after intracerebral infection. (B and C) No morphological differences or major differences in immune infiltrates could be detected between the groups receiving 1 × 106 (B) or 1 × 103 (C) OT-I CD8+ T cells (n = 4 mice per group). Scale bars, 1 mm. (D and E) Micrographs of periventricular areas in (D) and (E) represent the squares in (B) and (C) and have been stained using anti-CD8 mAb (gray), Hoechst for nuclei (blue), and OT-I cells expressing GFP (green). Scale bars, 20 μm. Bars next to the micrographs represent the clonal distribution of CD8+ T cells. (F) Overall numbers of CD8+ T cell clones per field of view in periventricular regions of brains from mice receiving transfers of 1 × 106 (HI) or 1 × 103 (LO) OT-I CD8+ T cells. *P < 0.05, two-way ANOVA.
Gustaf Christoffersson et al. Sci. Immunol. 2018;3:eaam6533
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