Upper-respiratory infection triggers experimental autoimmune encephalomyelitis onset in autoimmune prone t-cell receptor transgenic mice

Blackmore, Stephen Daniel

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https://hdl.handle.net/2142/95505 Copy

Description

Title

Upper-respiratory infection triggers experimental autoimmune encephalomyelitis onset in autoimmune prone t-cell receptor transgenic mice

Author(s)

Blackmore, Stephen Daniel

Issue Date

2016-12-05

Director of Research (if dissertation) or Advisor (if thesis)

Steelman, Andrew J.

Committee Member(s)

• Gaskins, H. Rex
• Johnson, Rodney
• Loerch, Steven
• Rodriguez-Zas, Sandra

Department of Study

Animal Sciences

Discipline

Animal Sciences

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• Multiple Sclerosis
• Experimental Autoimmune Encephalomyelitis
• Inflammation

Abstract

Multiple Sclerosis (MS) is an autoimmune-mediated demyelinating and neurodegenerative disease of the central nervous system. Most MS patients experience a disease course characterized by periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Relapse contributes to disability but the processes that trigger relapses are poorly understood. Upper-respiratory viral infection increases the risk for relapse. Here, we tested the hypothesis that upper respiratory infection is sufficient to cause glial activation, promote immune cell trafficking to the CNS and trigger pathology in an autoimmune-prone T cell receptor transgenic mouse line. To test this hypothesis we infected 2D2 mice and monitored for symptoms of inflammatory demyelination (EAE). Clinical and histological EAE was observed in ~29.2% of infected 2D2 mice which closely resembles the incidence of upper-respiratory infection-induced relapse in MS patients. Chemokine production in brain resident glial cells, primarily astrocytes was induced by TNF and IL-1β stimulation which may assist in the trafficking of immune cells to the CNS. Furthermore, pharmacological inhibitors of JNK, ERK1/2, p38, and NF-κB modulated the levels of chemokines secreted by astrocytes in response to cytokine stimulation. Increased levels of serum IFN-γ were observed in C57BL/6 mice infected with influenza as well as increased CD4+ T-cells in the choroid plexus. Finally, we observed immunosurveillance of the brain by T-cells and CD45highCD11b+ cells in C57BL/6 mice after influenza inoculation. This immunosurveillance could prove detrimental to MS patients.

Graduation Semester

2016-12

Type of Resource

text

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http://hdl.handle.net/2142/95505

Copyright and License Information

Copyright 2016 Stephen Blackmore

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