Contribution of T cells to the development of autoimmune diabetes in the NOD mouse model.
The nonobese diabetic (NOD) mouse spontaneously develops an autoimmune diabetes that shares many immunogenetic features with human insulin-dependent diabetes mellitus (IDDM), type 1 diabetes. The mononuclear cell infiltrates in the islet, which results in the development of insulitis (a prerequisite step for the development of diabetes) are primarily composed of T cells. It is now well accepted that these T cells play important roles in initiating and propagating an autoimmune process, which in turn destroys insulin-producing islet beta cells in the pancreas. T cells are subdivided into CD4+ helper T cells and CD8+ cytotoxic T cells. CD4+ T cells are further subdivided into Th1 and Th2 cells based on profiles of cytokine production, and these two T-cell populations counterregulate each other. Because many autoimmune diseases are Th1 T-cell mediated, current studies have focused on manipulating the Th1/Th2 imbalance to suppress the autoimmune process in the NOD model. Furthermore, the incidence of disease is much higher in females than that in males, suggesting an involvement of sex-steroid hormones in the development of diabetes. Understanding insights of the mechanism of immune-mediated islet cell destruction and the interaction between the immune and the neuroendocrine system may, therefore, provide new therapeutic means of preventing this chronic debilitating disease.
Toyoda
H
H
Department of Medicine, UCLA School of Medicine, Cedars-Sinai Medical Center 90048, USA.
Formby
B
B
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D007249:Inflammation; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics / Q000276:immunology*; D015213:Neuroimmunomodulation; D011236:Prediabetic State / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D012739:Gonadal Steroid Hormones