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Title: Variability in the immune response to Theiler's murine encephalomyelitis virus in different strains of mice
Author: MacDonald, N. C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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In this study mRNA transcript levels for numerous cytokines were studied in the brains and spinal cords in Balb/c (resistant), CBA (intermediately susceptibility) and SJL/J (susceptible) mice, during the acute phase of disease, using the technique of RNase protection assay. The RPA included analysis for transcripts for TNFβ, TNFα, TGFβ, IFNγ, IL-1α, IL-1β, IL-2, IL4, IL-5, IL-6, IL-7, IL-10, IL-13, IL-12p40 and IL-12p35. There were similarities between the strains in the levels of pro-inflammatory cytokines expressed including TNFα, TNFβ and IL1α. However, there were several fundamental differences between the strains including the inability of susceptible SJL/J mice to express IL-1β in the brains and the spinal cord when compared to Balb/c and CBA mice. SJL/J mice had an increase in expression of IL-4 and IL-10 and a decrease in expression of IL-2 and IFNγ when compared to Balb/c and CBA mice. Expression of pro-inflammatory, anti-inflammatory, Thl and Th2 type cytokines correlated with the increase in levels of cellular infiltrates (CD3+, CD4+, CD8+ and F4/80+) in the CNS. Anti-viral immunoglobulin isotypes were also different in the three mouse strains studied. All strains produced similar levels of IgM however, Balb/c mice had significantly increased levels of IgG1 and IgG2a compared to CBA and SJL/J mice during the acute phase of disease. This study also investigated TMEV persistence in CBA (intermediately susceptible) mice and the cytokine and anti-viral immunoglobulin isotypes associated with persistence. Virus persisted for >60 days in 50% of infected CBA mice, as determined by RT-PCR. Animals in which virus persisted had significantly increased RNA transcripts in the CNS for TNFα, IL-12p35 and IL-12p40. Persistently infected animals also had increased levels of anti-viral IgG1, IgG2a and IgG2b when compared to animals which had cleared the virus.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available