A noncytolytic IL-10/Fc fusion protein prevents diabetes, blocks autoimmunity, and promotes suppressor phenomena in NOD mice.
A noncytolytic IL-10/Fc fusion protein prevents diabetes, blocks autoimmunity, and promotes suppressor phenomena in NOD mice.
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DOI：
10.4049/jimmunol.158.9.4507
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发表时间：
1997-05
影响因子：
4.4
通讯作者：
X. Zheng;A. Steele;Wayne W. Hancock;A. Stevens;Peter W. Nickerson;Prabir Roy-Chaudhury;Y. Tian;Terry B. Strom
中科院分区：
文献类型：
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作者：
X. Zheng;A. Steele;Wayne W. Hancock;A. Stevens;Peter W. Nickerson;Prabir Roy-Chaudhury;Y. Tian;Terry B. Strom
我们已经成功地在我们的努力，以开发一个长寿命的非细胞溶解性鼠IL-10/Fc融合蛋白。在非肥胖糖尿病小鼠（NOD）模型中，从5至25周龄给予IL-10/Fc完全防止了糖尿病的发生。此外，这些小鼠在IL-10/Fc治疗停止后很长时间内保持无疾病。免疫组织化学研究表明，IL-10/Fc治疗抑制TNF-α（促炎细胞因子）以及Th 1型细胞因子IL-2和IFN-γ的表达，但促进胰岛浸润白细胞表达IL-4和IL-10（Th 2型细胞因子）。在NOD小鼠的糖尿病过继转移模型中，我们发现：1）IL-10/Fc处理的宿主携带阻断糖尿病表达的白细胞，2）这些白细胞甚至在IL-10/Fc处理停止后8周仍持续存在。IL-10/Fc在NOD模型中提供的有效抗糖尿病作用及其明显缺乏全身毒性是值得注意的。
We have been successful in our efforts to develop a long lived noncytolytic murine IL-10/Fc fusion protein. In the nonobese diabetic mouse (NOD) model, administration of IL-10/Fc from 5 to 25 wk of age completely prevented the occurrence of diabetes. Moreover, these mice remained disease-free long after cessation of IL-10/Fc therapy. Immunohistochemistry studies show that IL-10/Fc treatment inhibits expression of TNF-alpha, proinflammatory cytokine, as well as Th1-type cytokines, IL-2 and IFN-gamma, but promotes expression of IL-4 and IL-10, Th2-type cytokines, by islet-infiltrating leukocytes. In an adoptive transfer model of diabetes in NOD mice, we found that: 1) IL-10/Fc treated hosts bear leukocytes that block expression of diabetes and 2) these leukocytes persisted even 8 wk after cessation of IL-10/Fc treatment. The potent antidiabetogenic effects provided by IL-10/Fc in the NOD model, together with its apparent lack of systemic toxicity, are notable.