【摘要】 目的:探讨CD4-CD8-T细胞(DNT细胞)在小鼠病毒性肝炎慢性化中的作用和机制。方法:C3H/Hej小鼠感染3型鼠肝炎病毒(MHV-3)建立了小鼠慢性肝炎模型。分离感染病毒5天后的小鼠脾脏细胞,利用磁珠法分选得到DNT细胞,通过小鼠尾静脉注射过继到同样感染MHV-3的小鼠,观察其生存率、组织炎症和病毒载量的变化,检测FasL表达情况。体外将DNT细胞与同来源的CD8+T淋巴细胞共培养观察其抑制效应。结果:实验发现,肝炎小鼠的生存率由23.3%提高到46.67%,肝脏组织炎症减轻,病毒载量无变化。体外实验DNT细胞高表达FasL,对CD8+细胞有特异性杀伤效应。结论:CD4-CD8-双阴性T细胞可以通过Fas/FasL途径对CD8+T细胞进行特异性杀伤,从而导致肝炎的慢性迁延。更多还原

【Abstract】 Objective: To investigate the role of CD4-CD8-T( DNT) cells in murine hepatitis virus type 3( MHV-3) induced chronic viral hepatitis in C3H / Hej mice. Methods: Mice were received MHV-3 intraperitoneally. Five days after MHV-3infection,the DNT were isolated using magnetic bead from spleen and injected to another MHV-3 infected mice via the tail vein.The survival time and liver histology were observed. Virus titers were determined in the liver tissue of MHV-3 infected C3H / Hej mice at various time points. The FasL expression of DNT cells were determined by flow cytometry. The cytotoxic effects of DNT cells on CD8+T cells were examined by non-radioactive cytotoxicity assay. Results: The adoptive transfer experiment demonstrated that DNT cells could lead to the dramatic increase in the survival rate of the recipient mice and amelioration in liver histology but could not affect the virus titer of liver tissue. FasL was highly expressed on the surface of MHV-3 specific DNT cells,and DNT cells showed significant cytotoxic effect on CD8+T cells. Conclusion: These data suggested that MHV-3 specific DNT cells could considerably limit the serious virus-mediated inflammatory responses in the liver of infected recipient mice,but not able to inhibit virus replication thus contribute to viral persistence in this model.更多还原