Monokine-producing cells predominate in the recruitment phase of NOD insulitis while cells producing Th1-type cytokines characterize the effector phase

Journal of Autoimmunity
B PilströmJ Böhme

Abstract

Cells infiltrating the Langerhans' islets of prediabetic NOD females were isolated from 6 weeks to 6 months of age. These cells were assayed at a single-cell level for production of eight different cytokines by intracellular immunofluorescent staining. Quiescent in vivo preactivated cells were detected by in vitro stimulation with PMA and ionomycin for 4 h. The cell recruitment phase, between 6 and 12 weeks of age, is predominated by production of the monokines IL-1alpha, IL-6, and TNF After stimulation IFN-gamma and occasional IL-10 and GM-CSF producing cells could also be observed. This cytokine pattern occurs simultaneously with increasing insulitis, and we suggest that these cytokines are important in attracting inflammatory cells to the islets and maintaining the inflammatory state. A high frequency of endocrine cells producing IL-6 during this period may denote a stress response caused by initial beta-cell destruction due to cytokines released by the inflammatory cells. During the effector phase, between 4 and 6 months, there is a characteristic Th1 cytokine profile with lymphocytes producing IL-2, IFN-gamma and TNF, supposedly TNF-beta. No IL-4 production could be detected and IL-10 was very rarely found, indicating the ...Continue Reading

Citations

Jul 17, 2001·Clinical Endocrinology·J D Bretz, J R Baker
Sep 7, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S A Brod
Aug 21, 2007·Diabetes Research and Clinical Practice·S BilgicG Deniz
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