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Little is known about the mechanisms of neurodegeneration in MSA. However, recent work has highlighted the important role of the immune system to the pathophysiology of other synuclein-related diseases such as Parkinson\u2019s disease. In this study, we investigated postmortem brain tissue from MSA patients and control subjects for evidence of immune activation in the brain. We found a significant increase of HLA-DR<jats:sup>+<\/jats:sup> microglia in the putamen and substantia nigra of MSA patient tissue compared to controls, as well as significant increases in CD3<jats:sup>+<\/jats:sup>, CD4<jats:sup>+<\/jats:sup>, and CD8<jats:sup>+<\/jats:sup> T cells in these same brain regions. To model MSA in vivo, we utilized a viral vector that selectively overexpresses \u03b1-syn in oligodendrocytes (Olig001-SYN) with &gt; 95% tropism in the dorsal striatum of mice, resulting in demyelination and neuroinflammation similar to that observed in human MSA. Oligodendrocyte transduction with this vector resulted in a robust inflammatory response, which included increased MHCII expression on central nervous system (CNS) resident microglia, and infiltration of pro-inflammatory monocytes into the CNS. We also observed robust infiltration of CD4 T cells into the CNS and antigen-experienced CD4 T cells in the draining cervical lymph nodes. Importantly, genetic deletion of TCR-\u03b2 or CD4 T cells attenuated \u03b1-syn-induced inflammation and demyelination in vivo. These results suggest that T cell priming and infiltration into the CNS are key mechanisms of disease pathogenesis in MSA, and therapeutics targeting T cells may be disease modifying.<\/jats:p>","DOI":"10.1007\/s00401-020-02126-w","type":"journal-article","created":{"date-parts":[[2020,1,29]],"date-time":"2020-01-29T01:02:20Z","timestamp":1580259740000},"page":"855-874","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":96,"title":["T cell infiltration in both human multiple system atrophy and a novel mouse model of the disease"],"prefix":"10.1007","volume":"139","author":[{"given":"Gregory P.","family":"Williams","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Marmion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey M.","family":"Schonhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asta","family":"Jurkuvenaite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woong-Jai","family":"Won","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Standaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey H.","family":"Kordower","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7054-2812","authenticated-orcid":false,"given":"Ashley S.","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,1,29]]},"reference":[{"key":"2126_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JPD-140491","volume":"5","author":"HE Allen Reish","year":"2015","unstructured":"Allen Reish HE, Standaert DG (2015) Role of alpha-synuclein in inducing innate and adaptive immunity in Parkinson disease. 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