Experimental Allergic Encephalomyelitis (EAE) is an autoimmune demyelinating disease of the central nervous system (CNS) with pathological and clinical features, including patterns of remission and relapse, reminiscent of the human disease Multiple Sclerosis (MS). EAE can be induced by immunization with myelin proteins in genetically susceptible rodents and can be adoptively transferred with CD4$ sp+$ T cells. In this thesis the mechanisms governing EAE induction in SJL/J mice were examined by flow cytometric analysis of the migration into the CNS of CD4$ sp+$ T cells labelled with a lipophilic fluorescent dye (PKH2). Selective retention was demonstrated within the CNS of myelin basic protein (MBP)-reactive CD4$ sp+$ T cell blasts, which were of a CD44$ sp{ rm high},$ CD45RB$ sp{ rm low},$ memory/effector phenotype and which expressed mRNA for IL-2 and IFN-$ gamma$ but not for IL-4. Mechanisms of immunoregulation were examined during remission and in mice preimmunized with irradiated T cells (T-cell-vaccination). A loss of CD4$ sp+$ T cells from the CNS was observed in animals that had remitted, but neither reversion of memory/effector phenotype nor increased numbers of regulatory CNS CD8$ sp+$ cells were observed. In vaccination experiments, evidence was obtained for rescue of background activation levels and enhanced proliferative responses to antigens within lymph nodes of vaccinated animals. The effector and regulatory mechanisms described in this thesis may further facilitate the development of effective T-cell-vaccination protocols for the control of cell-mediated autoimmune disease.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41126 |
| Date | January 1993 |
| Creators | Zeine, Rana |
| 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 (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001327522, proquestno: NN87875, Theses scanned by UMI/ProQuest. |
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