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The protective mechanism of complete Freund’s adjuvant in type 1 diabetes

University of British Columbia

Type 1 diabetes is a multi-factorial disease resulting from the destruction of β- cells in the islets of Langerhans of the pancreas, causing a serious derangement of glucose metabolism that can be fatal in patients deprived of insulin treatment. It has been reported that P-cell destruction in this disease is mainly mediated by self-reactive cytotoxic T lymphocytes (CTL). Previous studies have shown that a single injection of complete Freund's adjuvant (CFA) prevents diabetes in non-obese diabetic (NOD) mice, but the mechanism(s) of protection remain unclear. In this thesis I have shown that CFA immunization of both NOD mice as well as cyclophosphamideaccelerated NOD mice markedly reduced the incidence of diabetes and that this reduced incidence was associated with a decrease in the number of B-cell specific, autoreactive CTL. In addition, the adoptive transfer of diabetes into syngeneic NOD / SCID recipients was prevented by CFA immunization and the protective effects of CFA were lost when cells expressing the natural killer (NK) cell marker, asialo GM1 were removed from both donor cells and recipient mice. Returning a population of CD3-DX5+ cells to the adoptive transfer restored the protective effects of CFA . Therefore, NK cells mediate the protective effects of CFA possibly through the downregulation of autoreactive CTL and stimulation of NK cells represents a novel approach to the prevention of autoimmune diabetes.

Thesis/Dissertation

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2009-10-30

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http://hdl.handle.net/2429/14480

Pathology

University of British Columbia

UBCV

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