Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by leukocytic infiltration of the central nervous system (CNS) and demyelination and remission/relapse. It is induced by CD4$ sp{+}$ T cells. We used reverse transcriptase/polymerase chain reaction to analyse T cell and cytokine gene expression in the CNS of SJL/J mice with myelin basic protein-induced EAE. Undetectable in normal CNS and cerebrospinal fluid, the expression of CD3, IL-2, IFN-$ gamma$, and TNF$ alpha$ increased in EAE, correlating with disease severity, then dropped to background levels during remission. IL-2 and IFN-$ gamma$ were produced by CD4$ sp{+}$ CD45RB$ sp{ rm low}$ T cells isolated from LN and CNS. In contrast, TNF$ alpha$ was predominately made by macrophages and microglia in the CNS. Purified microglia from normal CNS were induced to express TNF$ alpha$ by activated TH1 supernatant, suggesting that TNF$ alpha$ expression by cells in the CNS could be regulated by cytokines from infiltrating T cells. IL-4 was not detectable in total CNS or in isolated CD4$ sp{+}$ CD45RB$ sp{ rm low}$ cells from the CNS, but was readily amplified from CD4$ sp{+}$ CD45RB$ sp{ rm low}$ LN T cells. This suggests an enrichment of TH1 cells in autoimmune CNS. / To determine the effect of IFN-$ gamma$ expression in the CNS, we produced transgenic mice using an IFN-$ gamma$ cDNA downstream of an MBP promoter. Expression of the transgene was CNS-specific. MHC class I was induced in the CNS of transgenic mice. Transgenic animals that were backcrossed up to 5 generations with SJL/J did not develop spontaneous pathology. However, when they were immunized with MBP in adjuvant, the penetrance of EAE was greater, symptoms were more severe, and the duration of the first episode significantly longer than in non-transgenic littermates, suggesting a role for IFN-$ gamma$ in the amplification and perpetuation of EAE.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41754 |
| Date | January 1993 |
| Creators | Renno, Toufic |
| 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: 001397593, proquestno: NN94706, Theses scanned by UMI/ProQuest. |
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