T helper type 1 and 2 cytokines mediate the onset and progression of type I (insulin-dependent) diabetes

WY Almawi, H Tamim, ST Azar - The Journal of Clinical …, 1999 - academic.oup.com
The Journal of Clinical Endocrinology & Metabolism, 1999academic.oup.com
Type I (insulin-dependent) diabetes mellitus (IDDM) is an autoimmune disease that results
from the destruction of insulin-secreting pancreatic islet β-cells by autoreactive cells and
their mediators. Although its exact cause is not completely understood, it is well established
that IDDM is associated with dysregulated humoral and cellular immunity, exemplified by
altered production of and response to macrophage-and T cell-derived cytokines and a shift
in T helper (Th) cell differentiation in favor of a pathogenic Th1 pathway. Th1 cytokines …
Type I (insulin-dependent) diabetes mellitus (IDDM) is an autoimmune disease that results from the destruction of insulin-secreting pancreatic islet β-cells by autoreactive cells and their mediators. Although its exact cause is not completely understood, it is well established that IDDM is associated with dysregulated humoral and cellular immunity, exemplified by altered production of and response to macrophage- and T cell-derived cytokines and a shift in T helper (Th) cell differentiation in favor of a pathogenic Th1 pathway. Th1 cytokines, including interleukin-2 and interferon-γ, induced isletβ -cell destruction directly by accelerating activation-induced cell death (apoptosis) and by up-regulating the expression of select adhesion molecules, Th1 cytokines facilitated the pancreatic homing of autoreactive leukocytes, hence enhancing β-cell destruction. More recently, a role for Th2 cytokines in IDDM pathogenesis was described. Accordingly, local production of Th2 cytokines, in particular interleukin-10, accelerated β-cell destruction by enhancing autoreactive cell infiltration of the pancreas (insulitis) through modulation of the release of other cytokines and by modulating the microvasculature. Whereas both Th1 and Th2 cytokines are present in peripheral T cells and in the pancreas in IDDM, the mechanism of action and the kinetics of a cell damage induced by Th1 and Th2 cytokines appeared to be distinct. Collectively, this supports the idea that IDDM is not an exclusive Th1-mediated disorder as was suggested, and that both Th1 and Th2 cells and their respective mediators participate and cooperate in inducing and sustaining pancreatic islet β-cell destruction in IDDM.
Oxford University Press