| First Author | Lees JR | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 11 | Pages | 2633-42 |
| PubMed ID | 18852291 | Mgi Jnum | J:141105 |
| Mgi Id | MGI:3815376 | Doi | 10.1084/jem.20080155 |
| Citation | Lees JR, et al. (2008) Regional CNS responses to IFN-gamma determine lesion localization patterns during EAE pathogenesis. J Exp Med 205(11):2633-42 |
| abstractText | The localization of inflammatory foci within the cerebellum is correlated to severe clinical outcomes in multiple sclerosis (MS). Previous studies of experimental autoimmune encephalomyelitis (EAE), a model of MS, revealed distinct clinical outcomes correlated with the capacity of the animal to produce IFN-gamma. Outcomes were linked to localization of inflammatory cells in either the spinal cord (wild type [WT]) or the cerebellum and brain stem (IFN-gamma deficient). We demonstrate, using an adoptive transfer system, that the ability of the central nervous system (CNS) to sense pathogenic T cell-produced IFN-gamma during EAE initiation determines the sites of CNS pathogenesis. Transfer of WT Th1 cells into IFN-gamma receptor-deficient mice results in pathogenic invasion of the brain stem and cerebellum with attendant clinical symptoms, which are identical to the disease observed after transfer of IFN-gamma-deficient T cells to WT hosts. Inflammation of the spinal cord associated with classical EAE is abrogated in both IFN-gamma-deficient systems. Cotransfer of CNS antigen-specific WT Th1 cells with IFN-gamma-deficient T cells is sufficient to restore spinal cord invasion and block cerebellar and brain stem invasion. These data demonstrate that interaction between IFN-gamma and host CNS cells during the initiation of EAE can selectively promote or suppress neuroinflammation and pathogenesis. |
