Prediction of autoimmune diabetes in the non-obese diabetic mouse by ex vivo analysis of autoreactive cytotoxic T lymphocytes
Year: 2003
Type: article
Abstract: Type 1 diabetes affects approximately 20 million people worldwide, with 120 new cases diagnosed each year in British Columbia.Although individuals with type 1 diabetes are kept alive with daily injections of insulin, this treatment is not a cure, and does not protect individuals from early mortality as a result of disease-associated complications.As potential therapy for treatment of individuals with type 1 diabetes, promising strategies include islet transplantation in patients with established disease, or the treatment of newly-diagnosed patients with drugs that interfere with the immune response.Unfortunately, at the time of diagnosis, most individuals with type 1 diabetes have lost the majority of pancreatic P-cells as a result of a prolonged immune attack by the body's "defense" system.The ability to predict those individuals that will develop diabetes prior to extensive P-cell loss would provide a larger window of opportunity for therapeutic intervention.In this thesis, work is presented that focuses on a population of T cells that is highly pathogenic to P-cells in the pancreas of non-obese diabetic mice, a model of type 1 diabetes.Using a novel reagent, the dynamics of this T cell population were studied in order to determine the role of these autoimmune cells in disease pathogenesis.Quantification of this T cell population in the peripheral blood during the pre-diabetic period permitted identification of those mice that would develop diabetes.These T cells were examined also following islet transplantation in order to determine whether their presence in the blood would be an effective means of monitoring islet graft health.As interventions for type 1 diabetes become more effective, identification of individuals prior to development of disease will be critical for implementing treatment to preserve beta cell mass.The principles and practices for monitoring pathogenic T cells outlined in this thesis suggest that upon identification of important autoantigens in human diabetes, prediction may be possible using these methods.
Source: Summit (Simon Fraser University)
Author: Jacqueline D. Trudeau
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2306026923