Progression of spontaneous autoimmune diabetes is associated with a switch in the killing mechanism used by autoreactive CTL

Author： Qin Huilian

Publisher： Oxford University Press

ISSN： 1460-2377

Source： International Immunology, Vol.16, Iss.11, 2004-11, pp. : 1657-1662

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Abstract

Autoimmune (type 1) diabetes mellitus results from the destruction of insulin-producing pancreatic -cells by T lymphocytes. -cell death that is induced by autoreactive CTL in diabetes involves both Fas/Fas ligand (FasL)- and perforin/granzyme-mediated pathways, although their relative contributions during the progression of the disease remain unknown. We demonstrate here that despite the preferential use of the Fas/FasL pathway for cytolysis of -cell targets, transgenic -cell-specific CTL were able to kill targets via the perforin pathway when triggered by a higher affinity stimulus. In addition, we show that the killing mechanism used by islet-associated CD8⁺ T cells from non-obese diabetic mice changed as the mice aged and correspondingly, with the stage of diabetes. These results provide direct evidence for age-related changes in the cytotoxic pathways used by diabetogenic T cells during the progression of autoimmune diabetes.