Peri-islet Schwann cells in the pathogenesis of type 1 diabetes.
Published: 2005
Language: eng
Number of pages: 212
Description: Type 1 Diabetes (TID) is an autoimmune disease that destroys insulin-producing beta-cells in the pancreatic islets of Langerhans, resulting in chronic hyperglycemia. Type 1 diabetics require lifelong treatment with exogenous insulin. However, complications such as neuropathy, retinopathy, kidney and cardiovascular disease eventually develop. The incidence of T1D is increasing worldwide, as are its healthcare costs---$118 B USD annually in North America. Preventing T1D is an attractive goal and toward this end it is necessary to understand its etiology.Autoimmune diseases are classified into two categories, organ specific and systemic. T1D and Multiple Sclerosis (MS) are both organ-specific autoimmune diseases as pancreatic beta-cells and central nervous system myelin are the main targets, respectively. It was surprising therefore that T1D and MS patients exhibit similar autoreactive T cell profiles and are at higher risk to develop both diseases. This suggests that these two autoimmune diseases may have shared pathoetiological characteristics. In order to investigate the underlying basis for the similarity between T1D and MS we studied the Nonobese Diabetic (NOD) mouse model and focused on the neuronal elements in the islets of Langerhans, rediscovering the peri-islet Schwann cell (pSC) and documenting its important role in T1D.Elucidating pSC involvement in T1D furthers our understanding of islet autoimmunity and may potentially provide earlier diagnostic markers, improved prediabetes staging and novel intervention strategies. The autoimmune targeting of glial cells, such as pSC and oligodendrocytes may be a linking factor in T1D and MS, respectively.pSC envelops each islet of Langerhans. We demonstrate destruction of pSC as an early event in spontaneous T1D, prior to T cell invasion of the beta-cell mass. This destruction is corroborated by cellular and humoral autoimmune responses to the pSC antigen GFAP in both NOD mice and human Type 1 diabetics and immunotherapy with this antigen can prevent NOD T1D. Islet homing and targeting of pSC is separable from beta-cell autoimmunity and a distinct component of the diabetic immune response. Mechanistically, cognate interaction with CD8+ T cells is sufficient for pSC killing with important ramifications in vivo, as pSC destruction accelerates beta-cell demise and progression to T1D.
Notes: Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5313.

Thesis (Ph.D.)--University of Toronto, 2005.

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