In vivo diabetogenic action of CD41+ T lymphocytes requires Fas expression and is independent of IL-1 and IL-18

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2011
Author
Wen, Li
Green, E. Allison
Stratmann, Thomas
Panosa, Anaïs
Gomis, Ramon
Eynon, Elizabeth E.
Flavell, Richard A.
Mezquita, Jovita A.
Mora Giral, Concepció
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Wen, Li; Green, E. Allison; Stratmann, Thomas; Panosa, Anaïs; Gomis, Ramon; Eynon, Elizabeth E.; ... Mora Giral, Concepció. (2011) . In vivo diabetogenic action of CD41+ T lymphocytes requires Fas expression and is independent of IL-1 and IL-18. European Journal of Immunology, 2011, vol. 41, núm. 5, p. 1344-51. https://doi.org/10.1002/eji.201041216.
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Abstract
CD4+ T lymphocytes are required to induce spontaneous autoimmune diabetes in the NOD (Non Obese Diabetic) mouse. Since pancreatic β cells upregulate Fas expression upon exposure to proinflammatory cytokines, we studied whether the diabetogenic action of CD4+ T lymphocytes depends on Fas expression on target cells. We assayed the diabetogenic capacity of NOD spleen CD4+ T lymphocytes when adoptively transferred into a NOD mouse model combining: a) Fas-deficiency, b) FasL-deficiency, and c) the SCID mutation. We found that CD4+ T lymphocytes require Fas expression in the recipients’ target cells to induce diabetes. IL-1β has been described as a key cytokine involved in Fas up-regulation on mouse β cells. We addressed whether CD4+ T cells require IL-1β to induce diabetes. We also studied spontaneous diabetes onset in NOD/ICE (Interleukin-1 Converting Enzyme) deficient mice, in NOD/IL-1β deficient mice, and CD4+ T cell-adoptively transferred diabetes into NOD/SCID IL-1β-deficient mice. Neither IL-1β nor IL-18 are required for either spontaneous or CD4+ T-cell adoptively transferred diabetes. We conclude that CD4+ T cell-mediated β cell damage in autoimmune diabetes depends on Fas expression, but not on IL-1β, unveiling the existing redundancy regarding the cytokines involved in Fas upregulation on NOD β cells in vivo.
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http://hdl.handle.net/10459.1/71127
DOI
https://doi.org/10.1002/eji.201041216
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European Journal of Immunology, 2011, vol. 41, núm. 5, p. 1344-51
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