T cells in experimental autoimmune encephalomyelitis
Citation:
Stephen Lalor, 'T cells in experimental autoimmune encephalomyelitis', [thesis], Trinity College (Dublin, Ireland). School of Biochemistry and Immunology, 2010, pp 364Download Item:
Abstract:
Multiple sclerosis (MS) is an intlammatory, demyelinating disease of the central nervous system (CNS) that is both clinically and pathologically heterogeneous. Studies in experimental autoimmune encephalomyelitis (EAE), an animal model for MS, have demonstrated that T cells specific for self antigens mediate pathology in these diseases. Th1 cells were thought to be the main effector T cells responsible for the autoimmune inflammation. However, recent studies have highlighted an important pathogenic role for CD4+ T cells that secrete interleukin (IL)-17, termed Th17 cells. IL-17 induces IL-I, tumour necrosis factor (TNF)-a and IL-6 expression in inflamed tissues, and IL-1, IL-6, IL-21 and IL-23 are thought to drive Th17 cell development in the presence of TGF-β. However, CD8+, γδ+ and natural killer (NK) T cells, neutrophils and microglia have also been found to secrete IL-17.
This study examined the time course and distribution of IL-17-producing T cells involved in the pathogenesis of EAE. Significant infiltration of CD4+ T cells and γδ+ T cells into the brain and spinal cord of mice was observed immediately prior to the onset of clinical signs of EAE. A high frequency of γδ T cells expressed IL-17, but not IFN-y, in the acute phase of disease. These cells were found to be CD27- and predominantly of the Vγ4 subset. IL-17 production by CD4+ Th17 cells was also significantly elevated at the onset of clinical signs and in the acute phase of disease. These findings correlated with increased expression of IL-17, IL-23, IL-1β, IL-6 and TGF-β mRNA in the cerebral cortex, cerebellum and spinal cord. Conversely, IL-17 expression, as well as that of IL- 1β, IL-6 and IL-23, was significantly upregulated in the spleens of mice 7 days after induction of EAE, and decreased thereafter. This coincided with a significant increase of Th17 cells in the spleen and lymph nodes at this stage. IL-17 expression by NK cells and CD8+ T cells did not change significantly over the course of disease.
Author: Lalor, Stephen
Advisor:
Mills, KingstonQualification name:
Doctor of Philosophy (Ph.D.)Publisher:
Trinity College (Dublin, Ireland). School of Biochemistry and ImmunologyNote:
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Full text availableKeywords:
Biochemistry, Ph.D., Ph.D. Trinity College DublinMetadata
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