Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus
The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is crit...
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| Format: | Article |
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7719 |
| _version_ | 1797550576342401024 |
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| author | Hyun Seok Kang Wanqiu Hou Byung S. Kim |
| author_facet | Hyun Seok Kang Wanqiu Hou Byung S. Kim |
| author_sort | Hyun Seok Kang |
| collection | DOAJ |
| description | The infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4<sup>+</sup> T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4<sup>+</sup> T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4<sup>+</sup> T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4<sup>+</sup> T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3<sup>+</sup>CD4<sup>+</sup> T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3<sup>+</sup>CD4<sup>+</sup> T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4<sup>+</sup> T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease. |
| first_indexed | 2024-03-10T15:31:19Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:31:19Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-311af20b6ff24cb4a42fe678aa61068e2023-11-20T17:36:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120771910.3390/ijms21207719Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s VirusHyun Seok Kang0Wanqiu Hou1Byung S. Kim2Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USADepartment of Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USAThe infection of susceptible mice with Theiler’s murine encephalomyelitis virus (TMEV) induces a T cell-mediated demyelinating disease. This system has been studied as a relevant infection model for multiple sclerosis (MS). Therefore, defining the type of T cell responses and their functions is critically important for understanding the relevant pathogenic mechanisms. In this study, we adoptively transferred naive VP2-specific TCR-Tg CD4<sup>+</sup> T cells into syngeneic susceptible SJL mice and monitored the development of the disease and the activation and proliferation of CD4<sup>+</sup> T cells during the early stages of viral infection. The preexisting VP2-specific naive CD4<sup>+</sup> T cells promoted the pathogenesis of the disease in a dose-dependent manner. The transferred VP2-specific CD4<sup>+</sup> T cells proliferated rapidly in the CNS starting at 2–3 dpi. High levels of FoxP3<sup>+</sup>CD4<sup>+</sup> T cells were found in the CNS early in viral infection (3 dpi) and persisted throughout the infection. Activated VP2-specific FoxP3<sup>+</sup>CD4<sup>+</sup> T cells inhibited the production of IFN-γ, but not IL-17, via the same VP2-specific CD4<sup>+</sup> T cells without interfering in proliferation. Thus, the early presence of regulatory T cells in the CNS with viral infection may favor the induction of pathogenic Th17 cells over protective Th1 cells in susceptible mice, thereby establishing the pathogenesis of virus-induced demyelinating disease.https://www.mdpi.com/1422-0067/21/20/7719virusdemyelinationinflammationTh cellsFoxP3<sup>+</sup>CD4<sup>+</sup> T cells |
| spellingShingle | Hyun Seok Kang Wanqiu Hou Byung S. Kim Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus International Journal of Molecular Sciences virus demyelination inflammation Th cells FoxP3<sup>+</sup>CD4<sup>+</sup> T cells |
| title | Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus |
| title_full | Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus |
| title_fullStr | Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus |
| title_full_unstemmed | Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus |
| title_short | Rapid Expansion of Virus-Specific CD4<sup>+</sup> T Cell Types in the CNS of Susceptible Mice Infected with Theiler’s Virus |
| title_sort | rapid expansion of virus specific cd4 sup sup t cell types in the cns of susceptible mice infected with theiler s virus |
| topic | virus demyelination inflammation Th cells FoxP3<sup>+</sup>CD4<sup>+</sup> T cells |
| url | https://www.mdpi.com/1422-0067/21/20/7719 |
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