Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen 45122, Germany.
J Immunol. 2011 Oct 1;187(7):3730-7. doi: 10.4049/jimmunol.1101612. Epub 2011 Aug 26.
It was recently reported that inhibitory molecules such as programmed death-1 (PD-1) were upregulated on CD8(+) T cells during acute Friend retrovirus infection and that the cells were prematurely exhausted and dysfunctional in vitro. The current study confirms that most activated CD8(+) T cells upregulated expression of PD-1 during acute infection and revealed a dichotomy of function between PD-1(hi) and PD-1(lo) subsets. More PD-1(lo) cells produced antiviral cytokines such as IFN-γ and TNF-α, whereas more PD-1(hi) cells displayed characteristics of cytotoxic effectors such as production of granzymes and surface expression of CD107a. Importantly, CD8(+) T cells mediated rapid in vivo cytotoxicity and were critical for control of acute Friend virus replication. Thus, direct ex vivo analyses and in vivo experiments revealed high CD8(+) T cell functionality and indicate that PD-1 expression during acute infection is not a marker of T cell exhaustion.
最近有报道称，在急性 Friend 逆转录病毒感染过程中，CD8(+) T 细胞上上调了抑制分子，如程序性死亡受体 1（PD-1），并且这些细胞在体外过早耗尽和功能失调。本研究证实，大多数活化的 CD8(+) T 细胞在急性感染期间上调 PD-1 的表达，并揭示了 PD-1(hi)和 PD-1(lo)亚群之间的功能二分法。更多的 PD-1(lo)细胞产生抗病毒细胞因子，如 IFN-γ和 TNF-α，而更多的 PD-1(hi)细胞表现出细胞毒性效应物的特征，如颗粒酶的产生和 CD107a 的表面表达。重要的是，CD8(+) T 细胞介导了体内的快速细胞毒性作用，并且对于控制急性 Friend 病毒复制至关重要。因此，直接的体外分析和体内实验揭示了高 CD8(+) T 细胞功能，并表明 PD-1 在急性感染期间的表达不是 T 细胞耗竭的标志物。
