{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T15:46:27Z","timestamp":1770479187536,"version":"3.49.0"},"reference-count":51,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,10,27]]},"abstract":"<jats:p>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-\u03b3. Outcomes were linked to localization of inflammatory cells in either the spinal cord (wild type [WT]) or the cerebellum and brain stem (IFN-\u03b3 deficient). We demonstrate, using an adoptive transfer system, that the ability of the central nervous system (CNS) to sense pathogenic T cell\u2013produced IFN-\u03b3 during EAE initiation determines the sites of CNS pathogenesis. Transfer of WT Th1 cells into IFN-\u03b3 receptor\u2013deficient 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-\u03b3\u2013deficient T cells to WT hosts. Inflammation of the spinal cord associated with classical EAE is abrogated in both IFN-\u03b3\u2013deficient systems. Cotransfer of CNS antigen-specific WT Th1 cells with IFN-\u03b3\u2013deficient T cells is sufficient to restore spinal cord invasion and block cerebellar and brain stem invasion. These data demonstrate that interaction between IFN-\u03b3 and host CNS cells during the initiation of EAE can selectively promote or suppress neuroinflammation and pathogenesis.<\/jats:p>","DOI":"10.1084\/jem.20080155","type":"journal-article","created":{"date-parts":[[2008,10,14]],"date-time":"2008-10-14T00:34:30Z","timestamp":1223944470000},"page":"2633-2642","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":148,"title":["Regional CNS responses to IFN-\u03b3 determine lesion localization patterns during EAE pathogenesis"],"prefix":"10.1084","volume":"205","author":[{"given":"Jason R.","family":"Lees","sequence":"first","affiliation":[{"name":"1Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201"}]},{"given":"Paul T.","family":"Golumbek","sequence":"additional","affiliation":[{"name":"2Departments of Neurology and Pediatrics"}]},{"given":"Julia","family":"Sim","sequence":"additional","affiliation":[{"name":"3Department of Developmental Biology,"}]},{"given":"Denise","family":"Dorsey","sequence":"additional","affiliation":[{"name":"3Department of Developmental Biology,"}]},{"given":"John H.","family":"Russell","sequence":"additional","affiliation":[{"name":"3Department of Developmental Biology,"},{"name":"4The Immunology Program, Washington University, St. Louis, MO 63110"}]}],"member":"291","published-online":{"date-parts":[[2008,10,13]]},"reference":[{"key":"2023072516093526800_BIB1","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000110190","volume":"8","year":"1989","journal-title":"Neuroepidemiology."},{"key":"2023072516093526800_BIB2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1177\/135245859900500205","volume":"5","year":"1999","journal-title":"Mult. 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