Green E A, Flavell R A
Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Immunity. 2000 May;12(5):459-69. doi: 10.1016/s1074-7613(00)80198-3.
The inflammatory cytokine tumor necrosis factor alpha (TNFalpha) has been linked to the development of several autoimmune diseases. By adapting the tetracycline-regulated gene transcription system, we generated a murine model where islet-specific expression of TNFalpha could be repressed/derepressed within 48 hr following introduction/removal of tetracycline in the drinking water. Here we describe the temporal importance of TNFalpha in diabetes development in mice expressing islet-specific B7-1 and TNFalpha. We show that the duration of TNFalpha-mediated inflammation, not the putative maturity of the immune system at the time of TNFalpha expression, determines diabetes progression. Further, we have described an interval between 21 and 25 days following initiation of TNFalpha expression where the fate of islet-reactive T cells is decided.
炎性细胞因子肿瘤坏死因子α（TNFα）与多种自身免疫性疾病的发生有关。通过采用四环素调控的基因转录系统，我们构建了一个小鼠模型，在饮用水中引入/去除四环素后的48小时内，胰岛特异性表达的TNFα能够被抑制/解除抑制。在此，我们描述了TNFα在表达胰岛特异性B7-1和TNFα的小鼠糖尿病发生过程中的时间重要性。我们发现，TNFα介导的炎症持续时间而非TNFα表达时免疫系统的假定成熟度决定了糖尿病的进展。此外，我们还描述了在TNFα表达开始后的21至25天之间存在一个时间段，在此期间胰岛反应性T细胞的命运被决定。
