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Autoaggressive T cells in insulin-dependent diabetes mellitus

Considerable evidence suggests that insulin-dependent diabetes mellitus (IDDM) is a T cell-mediated autoimmune process that is directed against antigenic target(s) on pancreatic $ beta$ cells. To better understand T cell involvement in the pathogenesis of IDDM, a panel of T cell hybridomas were produced from pancreas-derived T cells of spontaneously diabetic NOD mice. A total of 119 hybridomas were constructed from 8 fusions and 94 of these were tested. Twelve hybridomas were found to be islet-reactive since they produced high level of interleukin-2 (IL-2) in the presence of NOD islet cells and NOD antigen-presenting cells (APC's). The responses could also be detected against islet cells of other strains (i.e. C3H/Hej or C57B1/6), but only in the presence of the NOD APC's. Phenotyping of these islet-reactive hybridomas showed that all of them were CD3$ sp{+}$CD4$ sp{+}$. Furthermore, a high frequency (39%) of CD4$ sp{+}$ T hybridomas in the panel were found to be islet reactive. In addition, analysis of T-cell receptor (TCR) V$ sb{ beta}$ expression of these islet-reactive T-cell hybridomas revealed that TCR V$ sb{ beta}$ element usage is heterogeneous unlike findings in some experimentally induced autoimmune diseases.

Identiferoai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.60429
Date January 1990
CreatorsLong, Tianying
PublisherMcGill University
Source SetsLibrary and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada
LanguageEnglish
Detected LanguageEnglish
TypeElectronic Thesis or Dissertation
Formatapplication/pdf
CoverageMaster of Science (Department of Pathology.)
RightsAll items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated.
Relationalephsysno: 001213386, proquestno: AAIMM67565, Theses scanned by UMI/ProQuest.

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