Experimental autoimmune encephalomyelitis (EAE) is a central nervous system (CNS) disease, with symptoms reminiscent of Multiple Sclerosis. During disease, the CNS is infiltrated by immune cells, with increased expression of MHC antigens and Th1 cytokines. / We asked whether antigen presentation in the CNS controls the bias towards Th1 cytokine in mice. We examined the capability of microglia to act as antigen presenting cells. We found that they stimulated T cell responses in vitro, but supported increased production of Th1 cytokines only. We also found that IL-12 mRNA was upregulated during peak disease, produced by resident microglia. We therefore propose that microglia, through their production of IL-12, influence the cytokine response in the CNS to produce the observed Th1 bias. / We investigated the effect of deletion of IFN-gamma on the ability to induce EAE in genetically-resistant (BALB/c) mice. IFN-gamma-/- mice were susceptible to induction of EAE, and cellular infiltrates in the CNS showed increases in message for CD3 and TNF-alpha. Therefore, IFN-gamma converts an otherwise EAE-susceptible mouse strain to become EAE-resistant. / We examined whether the negative effect of IFN-gamma on generation of encephalitogenic T cells in the periphery might differ from its role in the CNS. We interbred IFN-gamma -/- mice to mice transgenically overexpressing IFN-gamma in the CNS. Levels of IFN-gamma in CNS of the resulting mice were insufficient to induce spontaneous disease. These mice will be useful tools for studying the role of IFN-gamma in CNS disease. / During EAE, T cells of many specificities infiltrate the CNS. The function of those that do not recognize CNS antigens ("bystanders") is unclear. We transferred Ovalbumin-reactive (bystander) T cells to mice prior to EAE onset. Flow cytometry analysis showed that the vast majority of myelin basic protein-reactive T cells in the CNS were memory/effector cells, but only very few bystander T cells showed an activated/memory/effector phenotype. As a whole population, the bystander cells did not upregulate their expression of CD44 or IL-2Ralpha, or production of IFN-gamma, thus are probably not contributing to the ongoing immune response during disease.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.34748 |
| Date | January 1997 |
| Creators | Krakowski, Michelle L. |
| Contributors | Owens, Trevor (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Microbiology and Immunology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001601761, proquestno: NQ44479, Theses scanned by UMI/ProQuest. |
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