Picarella D E, Kratz A, Li C B, Ruddle N H, Flavell R A
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510.
Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10036-40. doi: 10.1073/pnas.89.21.10036.
Tumor necrosis factor beta (TNF-beta) (lymphotoxin) may play an important role in the immune response and pathologic inflammatory diseases. Insulitis is an important early step in the development of insulin-dependent diabetes mellitus. To understand better the role of TNF-beta in the regulation of inflammation and type 1 diabetes, we produced transgenic mice in which the murine TNF-beta gene was regulated by the rat insulin II promoter. The transgene was expressed in the pancreas, kidney, and skin of transgenic mice. The expression of TNF-beta in the pancreas of transgenic mice resulted in a leukocytic inflammatory infiltrate consisting primarily of B220+ IgM+ B cells and CD4+ and CD8+ T cells. The insulitis is reminiscent of the early stages of diabetes, though the mice did not progress to diabetes.
肿瘤坏死因子β（TNF-β）（淋巴毒素）可能在免疫反应和病理性炎症疾病中发挥重要作用。胰岛炎是胰岛素依赖型糖尿病发展过程中的一个重要早期步骤。为了更好地理解TNF-β在炎症调节和1型糖尿病中的作用，我们培育了转基因小鼠，其中小鼠TNF-β基因由大鼠胰岛素II启动子调控。转基因在转基因小鼠的胰腺、肾脏和皮肤中表达。转基因小鼠胰腺中TNF-β的表达导致了主要由B220 + IgM + B细胞以及CD4 + 和CD8 + T细胞组成的白细胞炎性浸润。尽管这些小鼠没有发展成糖尿病，但这种胰岛炎让人联想到糖尿病的早期阶段。
