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Immunol."],"abstract":"<jats:p>Theiler\u2019s murine encephalomyelitis virus (TMEV) is the causative agent of TMEV-induced demyelinating disease (TMEV-IDD); a well-established animal model for the chronic progressive form of human multiple sclerosis (MS). In susceptible mice with an inadequate immune response, TMEV-IDD is triggered by virus persistence and maintained by a T cell mediated immunopathology. OT-mice are bred on a TMEV-resistant C57BL\/6 background and own predominantly chicken ovalbumin (OVA)-specific populations of CD8<jats:sup>+<\/jats:sup> T cells (OT-I) or CD4<jats:sup>+<\/jats:sup> T cells (OT-II), respectively. It is hypothesized that the lack of antigen specific T cell populations increases susceptibility for a TMEV-infection in OT-mice on a TMEV-resistant C57BL\/6 background. OT-I, OT-II, and C57BL\/6 control mice were infected intracerebrally with the TMEV-BeAn strain. Mice were scored weekly for clinical disease and after necropsy, histological and immunohistochemical evaluation was performed. OT-I mice started to develop progressive motor dysfunction between 7 and 21 days post infection (dpi), leading up to hind limb paresis and critical weight loss, which resulted in euthanasia for humane reasons between 14 and 35 dpi. OT-I mice displayed a high cerebral virus load, an almost complete absence of CD8<jats:sup>+<\/jats:sup> T cells from the central nervous system (CNS) and a significantly diminished CD4<jats:sup>+<\/jats:sup> T cell response. Contrarily, only 60% (12 of 20) of infected OT-II mice developed clinical disease characterized by mild ataxia. 25% of clinically affected OT-II mice (3 of 12) made a full recovery. 5 of 12 OT-II mice with clinical disease developed severe motor dysfunction similar to OT-I mice and were euthanized for humane reasons between 13 and 37 dpi. OT-II mice displayed only low virus-immunoreactivity, but clinical disease correlated well with severely reduced infiltration of CD8<jats:sup>+<\/jats:sup> T cells and the increased presence of CD4<jats:sup>+<\/jats:sup> T cells in the brains of OT-II mice. Though further studies are needed to reveal the underlying pathomechanisms following TMEV infection in OT mice, findings indicate an immunopathological process as a main contributor to clinical disease in OT-II mice, while a direct virus-associated pathology may be the main contributor to clinical disease in TMEV-infected OT-I mice.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1194842","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T05:39:23Z","timestamp":1684906763000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Ovalbumin-specific CD4+ and CD8+ T cells contribute to different susceptibility for Theiler\u2019s murine encephalomyelitis virus 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