IFN-γ-Induced Chemokines Synergize with Pertussis Toxin to Promote T Cell Entry to the Central Nervous System

摘要: Inflammation of the CNS, which occurs during multiple sclerosis and experimental autoimmune encephalomyelitis, is characterized by increased levels IFN-γ, a cytokine not normally expressed in CNS. To investigate role IFN-γ we used intrathecal injection replication-defective adenovirus encoding murine (AdIFNγ) to IFN-γ-deficient (GKO) mice. This method resulted stable, long-lived expression that could be detected cerebrospinal fluid using ELISA Luminex bead immunoassay. induced CNS message protein for chemokines CXCL10 CCL5, comparable those seen encephalomyelitis. Other (CXCL2, CCL2, CCL3) were induced. Mice lacking IFN-γR showed no response, control viral vector did induce chemokine expression. Chemokine was predominantly localized meningeal ependymal cells, also astrocytes microglia. IFN-γ-induced lead inflammation. However, when pertussis toxin given i.p. mice infected with vector, there dramatic increase number T lymphocytes flow cytometry. blood-derived immune cells occur alone, manifest as histologically detectable inflammatory pathology. These results show induces characteristic glial response itself insufficient promote inflammation, chemoattractant signals can synergize peripheral infectious stimulus drive cell entry into