Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice
Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice
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DOI：
10.1093/intimm/8.1.23
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发表时间：
1996-01-01
影响因子：
4.4
通讯作者：
Ryffel, B
中科院分区：
文献类型：
--
作者：
Eugster, HP;Muller, M;Ryffel, B
为了研究肿瘤坏死因子（tumor necrosis factor， TNF）和淋巴毒素（lymphophotoxin， LT）- α在免疫系统发育和功能中的作用，在小鼠体内采用同源重组同时灭活TNF和LT - α基因，这些突变小鼠对单核细胞增生李斯特菌感染高度敏感，对d -半乳糖胺（D-GalN）和脂多糖（LPS）联合诱导的内毒素休克具有抗性，其脾脏微结构紊乱。其特征是失去明确定义的边缘区，T和a细胞区域定义不清，MAdCAM-1缺失，ICAM-1、VCAM-1和Mac-1表达降低。外周淋巴结和Peyer’s斑块缺失，肠固有层IgA（+）浆细胞明显减少，淋巴增生伴明显淋巴细胞增多，基础Ig水平降低，肾小球Ig沉积，不同组织内皮细胞MHC I类抗原表达明显上调。对绵羊红细胞的原发性体液免疫反应显示IgG同型开关有缺陷，而对水疱性口炎病毒的免疫反应正常。细胞毒性T细胞反应减弱，但对牛痘、淋巴细胞性脉络丛脑膜炎病毒（LCMV-ARM）和LCMV-WE仍然有效。总之，Tnf和Lt α的联合失活证实了它们在免疫系统正常发育和功能中的重要作用。
To investigate the roles of tumor necrosis factor (TNF) and lymphotoxin (LT)-alpha in the development and function of the immune system, the Tnf and Lt alpha genes were simultaneously inactivated in mice by homologous recombination, These mutant mice are highly susceptible to Listeria monocytogenes infection and resistant to endotoxic shock induced by the combined administration of D-galactosamine (D-GalN) and lipopolysaccharide (LPS), Their splenic microarchitecture is disorganized, characterized by the loss of the clearly defined marginal zone, ill defined T and a cell areas, and absence of MAdCAM-1 and reduced ICAM-1, VCAM-1 and Mac-1 expression. They are devoid of peripheral lymph nodes and Peyer's patches, and show a strong reduction of IgA(+) plasma cells in the intestinal lamina propria, The alymphoplasia is accompanied by a marked a lymphocytosis and reduced basal Ig levels, Ig depositions in the renal glomerulus and a strong up-regulation of MHC class I antigen expression on endothelial cells of different tissues are observed. The primary humoral immune response towards sheep red blood cells reveals a defective IgG isotype switch, while that against vescicular stomatitis virus is normal, The cytotoxic T cell responses are attenuated, although still effective, against vaccinia, lymphocytic choriomeningitis virus (LCMV-ARM) and LCMV-WE. In conclusion, the combined inactivation of Tnf and Lt alpha confirms their essential role in the normal development and function of the immune system.