Körner H, Cook M, Riminton D S, Lemckert F A, Hoek R M, Ledermann B, Köntgen F, Fazekas de St Groth B, Sedgwick J D
Centenary Institute of Cancer Medicine and Cell Biology, Sydney, Australia.
Eur J Immunol. 1997 Oct;27(10):2600-9. doi: 10.1002/eji.1830271020.
Specialized roles for the pro-inflammatory cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) were characterized in TNF/LT alpha -/- and TNF -/- mice established by direct gene targeting of C57BL/6 ES cells. The requirement for LT early in lymphoid tissue organogenesis is shown to be distinct from the more subtle and varied role of TNF in promoting correct microarchitectural organization of leukocytes in LN and spleen. Development of normal Peyer's patch (PP) structure, in contrast, is substantially dependent on TNF. Only mice lacking LT exhibit retarded B cell maturation in vivo and serum immunoglobulin deficiencies. A temporal hierarchy in lymphoid tissue development can now be defined, with LT being an essential participant in general lymphoid tissue organogenesis, developmentally preceeding TNF that has a more varied and subtle role in promotion of correct spatial organization of leukocytes in LN and spleen PP development in TNF -/- mice is unusual, indicating that TNF is a more critical participant for this structure than it is for other lymphoid tissues.
通过对C57BL/6胚胎干细胞进行直接基因靶向建立的TNF/LTα -/-和TNF -/-小鼠，确定了促炎细胞因子肿瘤坏死因子（TNF）和淋巴毒素（LT）的特殊作用。结果表明，在淋巴组织器官发生早期，LT的需求与TNF在促进淋巴结（LN）和脾脏中白细胞正确的微结构组织方面更为细微和多样的作用不同。相比之下，正常派尔集合淋巴结（PP）结构的发育很大程度上依赖于TNF。只有缺乏LT的小鼠在体内表现出B细胞成熟延迟和血清免疫球蛋白缺乏。现在可以定义淋巴组织发育中的时间层次，LT是一般淋巴组织器官发生的重要参与者，在发育上先于TNF，TNF在促进LN和脾脏中白细胞正确的空间组织方面具有更多样化和微妙的作用。TNF -/-小鼠中PP的发育是不寻常的，这表明TNF对该结构比对其他淋巴组织更关键。
