Impaired CD8 T cell antiviral immunity following acute spinal cord injury
Abstract Background Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. He...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-05-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12974-018-1191-8 |
| _version_ | 1818602068099727360 |
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| author | Diana M. Norden John R. Bethea Jiu Jiang |
| author_facet | Diana M. Norden John R. Bethea Jiu Jiang |
| author_sort | Diana M. Norden |
| collection | DOAJ |
| description | Abstract Background Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI. Methods One week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus. Profiles of immune cell populations were analyzed before infection, and virus-specific CD8 T cell response was analyzed 7 days post-infection. Results Following intranasal infection, injured mice had prolonged recovery and significant weight loss. Importantly, expansion and effector functions of virus-specific CD8 T cells were decreased in injured mice. The compromised CD8 T cell response was associated with inflammation and stress responses initiated after injury. Regulatory mechanisms, including increased regulatory T cells (Tregs) and upregulated PD-1/PD-L1, were induced following SCI. Furthermore, we show that increased corticosterone (CORT) levels can inhibit CD8 T cells and that blocking CORT in vivo following SCI enhances CD8 T cell antiviral responses. Conclusions Our results show that mice with mid-thoracic SCI have impaired CD8 T cell function during the acute stage of injury, indicating that impaired antiviral responses occur rapidly following SCI and is not dependent on injury level. |
| first_indexed | 2024-12-16T13:01:24Z |
| format | Article |
| id | doaj.art-9ca224a821964339b1b874b280c45364 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-16T13:01:24Z |
| publishDate | 2018-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-9ca224a821964339b1b874b280c453642022-12-21T22:30:50ZengBMCJournal of Neuroinflammation1742-20942018-05-0115111110.1186/s12974-018-1191-8Impaired CD8 T cell antiviral immunity following acute spinal cord injuryDiana M. Norden0John R. Bethea1Jiu Jiang2Department of Biology, Drexel UniversityDepartment of Biology, Drexel UniversityDepartment of Biology, Drexel UniversityAbstract Background Spinal cord injury (SCI) disrupts essential neuroimmune communication, leading to severe immune depression. Previous studies confirmed immune dysfunction in mice with chronic SCI and following high thoracic level injury where sympathetic innervation of the spleen is disrupted. Here, we induced a mid-thoracic injury where integrity of the sympathetic response is maintained and investigated the antiviral T cell response to influenza virus after acute SCI. Methods One week following a contusion SCI at thoracic level T9, mice were infected intranasally with influenza virus. Profiles of immune cell populations were analyzed before infection, and virus-specific CD8 T cell response was analyzed 7 days post-infection. Results Following intranasal infection, injured mice had prolonged recovery and significant weight loss. Importantly, expansion and effector functions of virus-specific CD8 T cells were decreased in injured mice. The compromised CD8 T cell response was associated with inflammation and stress responses initiated after injury. Regulatory mechanisms, including increased regulatory T cells (Tregs) and upregulated PD-1/PD-L1, were induced following SCI. Furthermore, we show that increased corticosterone (CORT) levels can inhibit CD8 T cells and that blocking CORT in vivo following SCI enhances CD8 T cell antiviral responses. Conclusions Our results show that mice with mid-thoracic SCI have impaired CD8 T cell function during the acute stage of injury, indicating that impaired antiviral responses occur rapidly following SCI and is not dependent on injury level.http://link.springer.com/article/10.1186/s12974-018-1191-8Spinal cord injuryInfectionInfluenza virusCD8 T cells |
| spellingShingle | Diana M. Norden John R. Bethea Jiu Jiang Impaired CD8 T cell antiviral immunity following acute spinal cord injury Journal of Neuroinflammation Spinal cord injury Infection Influenza virus CD8 T cells |
| title | Impaired CD8 T cell antiviral immunity following acute spinal cord injury |
| title_full | Impaired CD8 T cell antiviral immunity following acute spinal cord injury |
| title_fullStr | Impaired CD8 T cell antiviral immunity following acute spinal cord injury |
| title_full_unstemmed | Impaired CD8 T cell antiviral immunity following acute spinal cord injury |
| title_short | Impaired CD8 T cell antiviral immunity following acute spinal cord injury |
| title_sort | impaired cd8 t cell antiviral immunity following acute spinal cord injury |
| topic | Spinal cord injury Infection Influenza virus CD8 T cells |
| url | http://link.springer.com/article/10.1186/s12974-018-1191-8 |
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