In vivo effects of cytokines on pancreatic β-cells in models of type I diabetes dependent on CD4 T lymphocytes

Abstract

CD4+ T cells can actively kill β-cells in type I diabetes as well as help CD8+ T cells become cytolytic. Cytokines have the potential to kill β-cells, or upregulate Fas on β-cells, and increase their susceptibility to FasL. We investigated the direct effects of cytokines on β-cells in perforin-deficient non-obese diabetic (NOD) mice and NOD4.1 TCR transgenic mice, two models in which CD8+ T cells play a less dominant role. Inhibiting the effects of cytokines by the overexpression of suppressor of cytokine signalling-1 (SOCS1) in β-cells did not reduce diabetes or insulitis in perforin-deficient NOD, NOD4.1 or interleukin (IL)-1 receptor-deficient NOD4.1 mice. SOCS1 overexpression prevented F..