The T helper type 2 (Th2) cell product interleukin 10 (IL-10) inhibits the proliferation and function of Th1 lymphocytes and macrophages (M phi). The nonobese diabetic mouse strain (NOD/Shi) develops a M phi and T cell-dependent autoimmune diabetes that closely resembles human insulin-dependent diabetes mellitus (IDDM). The objective of the present study was to explore the consequences of localized production of IL-10 on diabetes development in NOD/Shi mice. Surprisingly, local production of IL-10 accelerated the onset and increased the prevalence of diabetes, since diabetes developed at 5-10 wk of age in 92% of IL-10 positive I-A beta g7/g7, I-E- mice in first (N2) and second (N3) generation backcrosses between IL-10 transgenic BALB/c mice and (NOD/Shi) mice. None of the IL-10 negative major histocompatibility complex-identical littermates were diabetic at this age. Furthermore, diabetes developed in 33% of I-A beta g7/d, I-E+ N3 mice in the presence of IL-10 before the mice were 10 wk old. Our findings support the notion that IL-10 should not simply be regarded as an immunoinhibitory cytokine, since it possesses powerful, immunostimulatory properties as well. Furthermore, our observations suggest that beta cell destruction in NOD mice may be a Th2-mediated event.
Article|
April 01 1994
Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice.
L Wogensen,
L Wogensen
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
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M S Lee,
M S Lee
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
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N Sarvetnick
N Sarvetnick
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
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L Wogensen
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
M S Lee
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
N Sarvetnick
Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1994) 179 (4): 1379–1384.
Citation
L Wogensen, M S Lee, N Sarvetnick; Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice.. J Exp Med 1 April 1994; 179 (4): 1379–1384. doi: https://doi.org/10.1084/jem.179.4.1379
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