Perforin-Mediated Effector Function Within the Central Nervous System Requires IFN-γ-Mediated MHC Up-Regulation

摘要: CD8+ T cells infiltrating the CNS control infection by neurotropic JHM strain of mouse hepatitis virus. Differential susceptibility infected cell types to clearance perforin or IFN-γ uncovered distinct, nonredundant roles for these antiviral mechanisms. To separately evaluate each effector function specifically in context cells, pathogenesis was analyzed mice deficient both and (PKO/GKO) selectively reconstituted transfer cells. Untreated PKO/GKO were unable died lethal encephalomyelitis within 16 days, despite substantially higher accumulation compared with controls. Uncontrolled associated limited MHC class I up-regulation an absence II expression on microglia, coinciding decreased CD4+ infiltrates. from perforin-deficient wild-type donors reduced virus replication recipients. By contrast, IFN-γ-deficient donor did not affect replication. The inability perforin-mediated mechanisms coincided expression. These data only confirm direct activity but also demonstrate IFN-γ-dependent surface guarantee local tissues inherently low further imply that plays a crucial role regulating balance between oligodendrocytes, function, demyelination.