昆士兰大学Belz, Gabrielle T.研究团队的一项最新研究揭示了GFI1驱动的转录和表观遗传程序维持CD8⁺ T细胞的干性和持久性。这一研究成果发表在2025年5月15日出版的国际学术期刊《自然—免疫学》上。

长久记忆CD8⁺ T细胞对于控制持续性病毒感染至关重要。人们对保存记忆细胞的机制知之甚少。转录抑制因子GFI1的命运定位发现，GFI1在病毒特异性CD8⁺ T在干细胞记忆细胞和中枢记忆细胞中选择性表达。GFI1的缺失导致细胞增殖减少和记忆性T这反过来又导致无法维持抗原特异性CD8⁺ T慢性淋巴细胞性脉络丛脑膜炎病毒或小鼠巨细胞病毒感染后的细胞群。GFI1的消融导致记忆性CD8⁺ T细胞中转录因子EOMES和BCL-2的下调。EOMES的异位表达挽救了BCL-2的表达，但记忆CD8⁺ T的持久性细胞仅部分获救。这些发现强调了GFI1在记忆CD8⁺ T长期维持中的关键作用，持续感染的细胞通过维持其增殖潜能。

附：英文原文

Title: GFI1-driven transcriptional and epigenetic programs maintain CD8⁺ Tcell stemness and persistence

Author: Chaudhry, M. Zeeshan, Chen, Evelyn, Man, Hiu On, Jones, Aneesha, Denman, Renae, Yu, Huiyang, Huang, Qiutong, Ilich, Adrian, Schreuder, Jaring, Navarro, Severine, Tuong, Zewen K., Belz, Gabrielle T.

Issue&Volume: 2025-05-15

Abstract: Long-lived memory CD8+ Tcells are essential for the control of persistent viral infections. The mechanisms that preserve memory cells are poorly understood. Fate mapping of the transcriptional repressor GFI1 identified that GFI1 was differentially regulated in virus-specific CD8+ Tcells and was selectively expressed in stem cell memory and central memory cells. Deletion of GFI1 led to reduced proliferation and progressive loss of memory Tcells, which in turn resulted in failure to maintain antigen-specific CD8+ Tcell populations following infection with chronic lymphocytic choriomeningitis virus or murine cytomegalovirus. Ablation of GFI1 resulted in downregulation of the transcription factors EOMES and BCL-2 in memory CD8+ Tcells. Ectopic expression of EOMES rescued the expression of BCL-2, but the persistence of memory CD8+ Tcells was only partially rescued. These findings highlight the critical role of GFI1 in the long-term maintenance of memory CD8+ Tcells in persistent infections by sustaining their proliferative potential.

DOI: 10.1038/s41590-025-02151-5

Source: https://www.nature.com/articles/s41590-025-02151-5