Fig 4.

LCMV infection after CD8 T cell transduction. Transfer of corrected or WT CD8 T cells prevents mice from development of the HLH-like phenotype. CD8 T cells were transplanted into Prf^−/− mice. Four weeks later, transplanted mice and control animals were infected with LCMV. A-C, Serum IFN-γ level (Fig 4, A) and phenotype (Fig 4, B and C) of PBMCs were assessed in infected and uninfected Prf^−/− mice on day 8. D, Weight loss in untreated Prf^−/− mice after LCMV infection. E, Survival was monitored until day 30 and is depicted as a Kaplan-Meier curve. All infected Prf^−/− mice without prior transplantation and RV GFP CD8 cell–transplanted mice were culled between days 8 and 12. One mouse of each treatment group had HLH and had to be culled subsequently. F and G, Phenotype of splenocytes show an expansion of total CD8 T cells and gp33⁺ CD8 T cells in Prf^−/− mice, which is in line with the phenotype of PBMCs. Prior transplantation of corrected CD8 T cells shows a decrease in CD8/CD8 gp33 T-cell expansion. H, Hemoglobin levels in treated compared with untreated mice. Data are shown as medians ± interquartile ranges of all investigated animals. *P < .05. ns, Nonsignificant. I,Upper panel, Hematoxylin and eosin–stained splenic sections show deranged splenic architecture in Prf^−/− mice without corrective intervention, whereas in treated and B6 mice it is preserved. Lower panel, Hematoxylin and eosin–stained liver sections display inflammatory foci and periportal lymphocytic infiltrates in untreated infected mice, whereas treated mice show similar liver histology as uninfected mice. Representative sections are shown at a magnification of ×5 (spleen) and ×10 (liver).