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Nevertheless, neuroinflammation and CD8 T cell accumulation is frequently observed in postmortem brain tissue of patients with neurodegeneration. We therefore developed a murine model of brain atrophy using the Theiler's murine encephalomyelitis virus (TMEV) infection model of multiple sclerosis. We employ single major histocompatibility complex (MHC) class I molecule conditional knockout mice generated by our program to analyze the contribution of immune cell infiltration and onset of atrophy. TMEV infected C57BL\/6 mice that singularly express H\u20102K\n                    <jats:sup>b<\/jats:sup>\n                    or H\u20102D\n                    <jats:sup>b<\/jats:sup>\n                    were evaluated. TMEV infection of these mice resulted in ventricular atrophy at 14 d.p.i. However, H\u20102D\n                    <jats:sup>b<\/jats:sup>\n                    expressing mice presented with significantly greater and continuous ventricular atrophy compared to H\u20102K\n                    <jats:sup>b<\/jats:sup>\n                    expressing mice and MHC class I knockout control mice. Flow cytometric analysis revealed H\u20102D\n                    <jats:sup>b<\/jats:sup>\n                    expressing mice had greater brain infiltrating CD8 T cell responses at 7 and 28\u2009dpi which correlated with the extent of ventricular atrophy. Meanwhile, H\u20102K\n                    <jats:sup>b<\/jats:sup>\n                    and MHC class I knockout mice also had distinct positive correlations with ventricular atrophy and global neuroinflammation in general. These findings support the role of immune cell infiltration into the CNS as a putative mechanism of ventricular atrophy following TMEV infection, with the progressive enlargement of ventricular atrophy observed in H\u20102D\n                    <jats:sup>b<\/jats:sup>\n                    mice being associated with the presence of long\u2010lived memory CD8 T cells residing in the brain.\n                  <\/jats:p>","DOI":"10.1096\/fj.202501045r","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T03:28:36Z","timestamp":1750908516000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Dissection of Neurotropic Theiler's Murine Encephalomyelitis Virus Induced Brain Atrophy in Single\n                    <scp>MHC<\/scp>\n                    Class I Mice of\n                    <scp>C57BL<\/scp>\n                    \/6 Background"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6378-6575","authenticated-orcid":false,"given":"Katheryn M.","family":"Wininger","sequence":"first","affiliation":[{"name":"Neuroscience Program Mayo Clinic  Rochester Minnesota USA"},{"name":"Mayo Clinic Graduate School of Biomedical Sciences Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katayoun","family":"Ayasoufi","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Neurosurgery Duke University  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney","family":"Anani\u2010Wolf","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Destin T","family":"Hinson","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron J.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Neuroscience Program Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Immunology Mayo Clinic  Rochester Minnesota USA"},{"name":"Department of Molecular Medicine Mayo Clinic  Rochester Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2023.106230"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-39809-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.10.016"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01382-x"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00461-4"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/dmcn.13363"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-7091-1544-2_40"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00668"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2022.800383"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13337-023-00830-1"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0708-2"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04569-5"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2021.111575"},{"key":"e_1_2_9_15_1","first-page":"1327","article-title":"Are\u2010Related Total Gray Matter and White Matter Changes in Normal Adult Brain. 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