Journal article

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

Eveline Angstetra, Kate L Graham, Sarah Emmett, Nadine L Dudek, Rima Darwiche, Rochelle Ayala-Perez, Janette Allison, Pere Santamaria, Thomas WH Kay, Helen E Thomas

Immunology and Cell Biology | NATURE PUBLISHING GROUP | Published : 2009

Abstract

CD4(+) T cells can actively kill beta-cells in type I diabetes as well as help CD8(+) T cells become cytolytic. Cytokines have the potential to kill beta-cells, or upregulate Fas on beta-cells, and increase their susceptibility to FasL. We investigated the direct effects of cytokines on beta-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 beta-cells did not reduce diabetes or insulitis in perforin-deficient NOD, NOD4.1 or interleukin (IL)-1 receptor-deficient NOD4.1 mice. SOCS1 overe..

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