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University of Nebraska Medical Center

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Full-Text Articles in Molecular Biology

Il-10 Is Necessary And Sufficient For Autoimmune Diabetes In Conjunction With Nod Mhc Homozygosity., Myung-Shik Lee, Regula Mueller, Linda S. Wicker, Laurence B. Peterson, Nora Sarvetnick Jun 1996

Il-10 Is Necessary And Sufficient For Autoimmune Diabetes In Conjunction With Nod Mhc Homozygosity., Myung-Shik Lee, Regula Mueller, Linda S. Wicker, Laurence B. Peterson, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Contrary to expectations based on in vitro experiments, we previously found that pancreatic IL-10 did not inhibit autoimmune diabetes but accelerated it in an MHC-dependent manner. Therefore, the ability of IL-10 to overcome the absence of all non-MHC diabetes susceptibility (Idd) alleles was studied in transgenic mice expressing pancreatic IL-10 backcrossed to B10.H2g7 congenic mice, which have no Idd alleles other than NOD MHC (H2g7). IL-10 transgenic backcross 1 (BC1) mice with H2g7/g7 haplotype developed clear-cut insulitis and diabetes, but neither transgenic mice with the H2g/b haplotype nor nontransgenic BC1 mice did so. Further implicating IL-10 in autoimmune diabetes, anti-IL-10 …


Sensitization To Self (Virus) Antigen By In Situ Expression Of Murine Interferon-Gamma., Myung-Shik Lee, Matthias Von Herrath, Hans Reiser, Michael B.A. Oldstone, Nora Sarvetnick Feb 1995

Sensitization To Self (Virus) Antigen By In Situ Expression Of Murine Interferon-Gamma., Myung-Shik Lee, Matthias Von Herrath, Hans Reiser, Michael B.A. Oldstone, Nora Sarvetnick

Journal Articles: Regenerative Medicine

Autoimmune disease results from inflammatory destruction of tissues by aberrant self-reactive lymphocytes. We studied the autoimmune potential of T lymphocytes immunologically ignorant of viral antigens acting as self antigens and whether the host defense molecule IFN-gamma could stimulate these cells to cytotoxic competency. For this purpose, we produced double transgenic mice expressing pancreatic IFN-gamma as well as lymphocytic choriomeningitis virus (LCMV) nucleoprotein (NP) or glycoprotein (GP) antigen. 100% of the NP+/IFN-gamma+ mice became diabetic before 2 mo of age, while none of the NP single transgenic littermates and only 10% of IFN-gamma single transgenic littermates did. Strikingly, NP+/IFN-gamma+ mice spontaneously …


Production Of Interleukin 10 By Islet Cells Accelerates Immune-Mediated Destruction Of Beta Cells In Nonobese Diabetic Mice., Lise Wogensen, Myung-Shik Lee, Nora Sarvetnick Apr 1994

Production Of Interleukin 10 By Islet Cells Accelerates Immune-Mediated Destruction Of Beta Cells In Nonobese Diabetic Mice., Lise Wogensen, Myung-Shik Lee, Nora Sarvetnick

Journal Articles: Regenerative Medicine

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 …