PD-1/PD-L1抑制性通路在病毒性感染中的研究进展

杀伤性T细胞(CTL)是病毒感染过程中主要的效应细胞.在急性病毒性感染中,CTL细胞通过杀伤病毒感染的细胞,分泌抗病毒细胞因子从而有效清除病毒.而在慢性病毒感染过程中,病毒特异性CTL发生克隆耗竭,细胞数量少,细胞功能受损,分泌细胞因子能力下降.目前证明,CD28家族成员Programmed Death-1(PD-1)是一种重要的细胞表面分子,能够抑制CTL细胞功能,参与外周免疫耐受,维持T细胞克隆耗竭,保护机体不受免疫病理损伤.在慢性病毒性感染中,T细胞表面的PD-1与其受体PD-L1/2结合后,传递抑制性信号,下调外周T细胞功能.阻断PD-1通路,能够重建CD8+T细胞功能,抑制病毒复制,促进病毒清除.因此,通过干扰PD-1/PD-L1抑制途径进行免疫调节,可能是处理慢性病毒感染性疾病的一个新方法.

The PD-1/PD-L1 Inhibit Pathway in the Viral Infection

Cytotoxic T lymphocyte(CTL)is the most important effector cell type for the control of viral in-fection.In acute infection.specific CTLs effectively contribute to the viral clearance by destruction of virus infected ceUs and producton of antiviral cytokines.However,specific CTLs may be exhausted daring chronic viral infections with impaired functions like suppressed cytokine predutions.Recent studies demonstrated that Programmed Death-1(PD-1),a member of CD28 family,is an important factor that inhibits the function of CTLs and plays a role in the peripheral immunological tolerance.It takes part in the maintenance of T cell exhaustion and protects the host against immunopathegenesis.T-cells receive a negative signal when engaged with the PD-L1 ligand on the APC.This mechanism is responsible for the down-regulation of T-cell functions in the periphery during chronic viral infections.By blocking the PD-1/PD-L1 pathway.the function of CD8+ T cell could be restored,leading to the suppression of viral replication in chronically infected hosts.Thus,the immunomodulation by interfering with PD-1/PD-L1 pathway represents a new way to treat chronic viral infections.