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The PD-1 Pathway Regulates Development and Function of Memory CD8+ T Cells following Respiratory Viral Infection.
Cell Reports ( IF 7.5 ) Pub Date : 2020-06-30 , DOI: 10.1016/j.celrep.2020.107827
Kristen E Pauken 1 , Jernej Godec 2 , Pamela M Odorizzi 3 , Keturah E Brown 1 , Kathleen B Yates 4 , Shin Foong Ngiow 3 , Kelly P Burke 5 , Seth Maleri 1 , Shannon M Grande 1 , Loise M Francisco 1 , Mohammed-Alkhatim Ali 3 , Sabrina Imam 4 , Gordon J Freeman 6 , W Nicholas Haining 7 , E John Wherry 3 , Arlene H Sharpe 8
Affiliation  

The PD-1 pathway regulates dysfunctional T cells in chronic infection and cancer, but the role of this pathway during acute infection remains less clear. Here, we demonstrate that PD-1 signals are needed for optimal memory. Mice deficient in the PD-1 pathway exhibit impaired CD8+ T cell memory following acute influenza infection, including reduced virus-specific CD8+ T cell numbers and compromised recall responses. PD-1 blockade during priming leads to similar differences early post-infection but without the defect in memory formation, suggesting that timing and/or duration of PD-1 blockade could be tailored to modulate host responses. Our studies reveal a role for PD-1 as an integrator of CD8+ T cell signals that promotes CD8+ T cell memory formation and suggest PD-1 continues to fine-tune CD8+ T cells after they migrate into non-lymphoid tissues. These findings have important implications for PD-1-based immunotherapy, in which PD-1 inhibition may influence memory responses in patients.



中文翻译:

PD-1 通路调节呼吸道病毒感染后记忆 CD8+ T 细胞的发育和功能。

PD-1 通路在慢性感染和癌症中调节功能失调的 T 细胞,但该通路在急性感染期间的作用仍不清楚。在这里,我们证明了最佳记忆需要 PD-1 信号。PD-1 通路缺陷的小鼠在急性流感感染后表现出 CD8 + T 细胞记忆受损,包括病毒特异性 CD8 + T 细胞数量减少和回忆反应受损。启动期间的 PD-1 阻断导致感染后早期的相似差异,但没有记忆形成的缺陷,这表明可以调整 PD-1 阻断的时间和/或持续时间来调节宿主反应。我们的研究揭示了 PD-1 作为 CD8 + T 细胞信号的整合者的作用,可促进 CD8 +T 细胞记忆形成并表明 PD-1 在 CD8 + T 细胞迁移到非淋巴组织后继续微调。这些发现对基于 PD-1 的免疫疗法具有重要意义,其中 PD-1 抑制可能会影响患者的记忆反应。

更新日期:2020-06-30
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