GFI1-driven transcriptional and epigenetic programs maintain CD8+ T cell stemness and persistence
Year: 2025
Type: article
Abstract: Long-lived memory CD8 + T cells 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 + T cells and was selectively expressed in stem cell memory and central memory cells. Deletion of GFI1 led to reduced proliferation and progressive loss of memory T cells, which in turn resulted in failure to maintain antigen-specific CD8 + T cell 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 + T cells. Ectopic expression of EOMES rescued the expression of BCL-2, but the persistence of memory CD8 + T cells was only partially rescued. These findings highlight the critical role of GFI1 in the long-term maintenance of memory CD8 + T cells in persistent infections by sustaining their proliferative potential.
Source: Nature Immunology
Authors: M. Zeeshan Chaudhry, Evelyn Chen, Hiu On Man, Aneesha Jones, Renae Denman, Huiyang Yu, Qiutong Huang, Adrian Ilich, Jaring Schreuder, Severine Navarro, Zewen K. Tuong, Gabrielle T. Belz
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,690
Awards: Understanding the circadian regulation of the innate lymphoid cells, Harnessing immune cell programs to drive immune protection , G3810071479, Determining regulators of ILC3 in mucosal barrier function and immune homeostasis, G4260407517, Understanding the Immune Response, G639929522, G6655665480, G717391505, Delineating immune circuits for innate and adaptive immune protection
OpenAlex ID: W4410412300