To examine the pathophysiological consequences of autoimmunity to TAG-1, CD4<sup>+</sup> T cells and autoantibodies specific for TAG-1 were generated and their potential to induce EAE was investigated in a rat model. An adoptive transfer of T cells specific for the first two immunoglobulin domains of TAG-1 initiates an intense inflammatory response in both the cortex and spinal cord in the Dark Agouti and Lewis rats. This is particularly interesting as conventional models of EAE are of little help in investigating the pathomechanisms responsible for cortical tissue damage, as the cortex is only rarely targeted by myelin-specific autoimmune responses in this animal model of Multiple Sclerosis (MS). Moreover, when a demyelinating antibody like Z2 (anti-MOG) antibody was co-transferred with TAG-1-specific T cells it resulted in demyelination not only in the spinal cord white matter but also the grey matter and triggered demyelination coupled with macrophage infiltration in the perivascular areas of the cortex. This new model of cortical demyelination is exciting as it bears some resemblance with chronic progressive MS. However, two different monoclonal antibodies (4D7/TAG1) and 3.1C12) specific to TAG-1, when co-transferred with TAG-1 specific T cells, failed to mediate tissue damage in the CNS. Although the role of TAG-1-specific antibodies in EAE remained inconclusive from the preliminary experiments, this study clearly demonstrates TAG-1-specific T cells as a new tool to mediate EAE highlighting cortical pathology which can be exploited further to investigate the factors that control regional differences in the pathogenesis of inflammatory demyelinating lesions in the CNS. This new model might provide novel insights into the development of cortical pathology in MS patients and will ultimately guide to design therapeutic approaches in MS.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:499706 |
| Date | January 2009 |
| Creators | Parikh, Khyati |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25214 |
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