Hsu H C, Zhou T, Yang P A, Herrera G A, Mountz J D
Department of Medicine, University of Alabama at Birmingham, and the Birmingham Veterans Administration Medical Center, 35294, USA.
J Immunol. 1997 Jun 15;158(12):5988-96.
We previously demonstrated that increased Fas expression in T cells of aged CD2-fas transgenic (Fas-Tg) CD-1 mice results in an increased immune response and T cell apoptosis. Surprisingly, despite prevention of T cell immune senescence, the average life span of Fas-Tg mice is comparable with that of nontransgenic (non-Tg) mice. Histopathologic evaluation of tissue sections showed that nearly 50% of the aged (>18-mo-old) Fas-Tg mice developed renal amyloid A amyloidosis, whereas no amyloid deposition was observed in aged non-Tg mice. The amyloid A deposition was observed primarily in glomeruli by using immunohistochemical stains and electron microscopy. The full-length amino acid coding sequence of serum amyloid A2 cDNA in CD-1 mice was identical to that of amyloid A amyloidosis-susceptible BALB/c mice. Although there was no significant difference in steady-state serum amyloid A level in the serum of aged non-Tg and Fas-Tg mice, challenging mice with staphylococcal enterotoxin B resulted in significantly higher serum levels of serum amyloid A on day 2 and IL-6 on days 1 and 2 and a higher magnitude of weight loss on day 7 in aged Fas-Tg mice compared with young mice. These parameters, at the indicated time points, were equivalent between young and aged non-Tg mice. Taken together, our data suggest that prevention of T cell senescence in Fas-Tg mice may be a factor in induction of an excessive acute-phase response triggered by T cell activation. The Fas-Tg mice are a novel model for understanding the immunologic mechanisms leading to secondary amyloidosis.
我们之前证明，在衰老的CD2-fas转基因（Fas-Tg）CD-1小鼠的T细胞中，Fas表达增加会导致免疫反应增强和T细胞凋亡。令人惊讶的是，尽管预防了T细胞免疫衰老，但Fas-Tg小鼠的平均寿命与非转基因（non-Tg）小鼠相当。组织切片的组织病理学评估显示，近50%的老年（>18月龄）Fas-Tg小鼠发生了肾淀粉样蛋白A淀粉样变性，而老年non-Tg小鼠未观察到淀粉样蛋白沉积。通过免疫组织化学染色和电子显微镜观察，淀粉样蛋白A沉积主要见于肾小球。CD-1小鼠血清淀粉样蛋白A2 cDNA的全长氨基酸编码序列与易患淀粉样蛋白A淀粉样变性的BALB/c小鼠相同。尽管老年non-Tg和Fas-Tg小鼠血清中稳态血清淀粉样蛋白A水平无显著差异，但用葡萄球菌肠毒素B攻击小鼠后，与年轻小鼠相比，老年Fas-Tg小鼠在第2天血清淀粉样蛋白A水平显著升高，在第1天和第2天IL-6水平显著升高，在第7天体重减轻幅度更大。在指定的时间点，这些参数在年轻和老年non-Tg小鼠之间是相当的。综上所述，我们的数据表明，Fas-Tg小鼠中T细胞衰老的预防可能是T细胞激活引发过度急性期反应的一个因素。Fas-Tg小鼠是理解导致继发性淀粉样变性的免疫机制的一种新模型。
