B细胞和T细胞亚型在海人藻酸引起的C57BL/6鼠海马神经元损伤过程中不同的作用

目的应用海人藻酸在C57BL/6免疫缺陷小鼠建立了神经退行性病变并观察了免疫活性B细胞和T细胞亚型在病变过程中的作用。方法经鼻滴人海人藻酸观察其临床和病理变化、细胞流式仪检测和分析脾细胞表面标记。结果海人藻酸引起了CD_4基因敲除(CD_4-/-)、CD_8(CD_8-/-)、CD_(48)(CD_(48)-/-)和B细胞(Igh6-/-)基因敲除鼠的临床抽搐症状和海马损伤。其临床症状在CD_4(-/-)鼠最重,CD_8(-/-),Igh6(-/-)以及野生型鼠次之,而CD_4、CD_8双重基因缺陷鼠最轻。病理变化大约和临床症状相平行,脾细胞表面标记的表达也证实了上述发现。结论获得性免疫反应参与了海人藻酸引起的海马损伤。CD_4T细胞和B细胞在病变过程中可能起到了保护作用,而CD8T细胞则加重神经退行性病变。

B cell and T cell subsets contribute differently to the pathogenesis that the KA-induced hippocampal neurodegeneration in C57BL/6 mice

Objective To study the roles of B cell and T cell subsets in Kainic acid(KA) induced neurodegen- eration of hippocampus.Methods KA was administrated by intranasal route into C57/BL/6 immune deficient mice.The clinical signs and the neuropathological change of hippocampus as well as molecule expression were ob- served.Results CD_4/CD_8(-/-) mice had the mildest seizures;the responses of CD_8(-/-),Igh-6(-/-) and wild-type mice were intermediate,whereas CD_4(-/-) mice displayed much more severe clinical signs and 100% early mortali- ty.Histopathological analysis of the mice that survived 7 days after KA administration revealed that CD_4/CD_8(-/-) mice had the fewest pathologic changes but that Igh-6(-/-) mice showed more severe lesions in area CA_3 of the hip- pocampus than CD_8(-/-) and wild-type mice.Numbers of splenic CD_4 T cells were increased in CD_8(-/-) and wild- type mice.CD_8 T cells were upregulated in Igh-6 (-/-) mice,and B cells rose numerically in CD_4 (-/-) mice. Conclusion Adaptive immune response is involved in the KA-induced hippocampal neurodegeneration in mice and suggests that B cell and T cell subsets contribute differently to the pathogenesis.