Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer

Oluwagbemiga A. Ojo, Hongxing Shen, Jennifer T. Ingram, James A. Bonner, Robert S. Welner, Georges Lacaud, Allan J. Zajac and Lewis Z. Shi ()
Additional contact information
Oluwagbemiga A. Ojo: University of Alabama at Birmingham
Hongxing Shen: University of Alabama at Birmingham
Jennifer T. Ingram: University of Alabama at Birmingham
James A. Bonner: University of Alabama at Birmingham
Robert S. Welner: University of Alabama at Birmingham
Georges Lacaud: The University of Manchester
Allan J. Zajac: University of Alabama at Birmingham
Lewis Z. Shi: University of Alabama at Birmingham

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract During chronic infection and tumor progression, CD8+ T cells lose their effector functions and become exhausted. These exhausted CD8+ T cells are heterogeneous and comprised of progenitors that give rise to effector-like or terminally-exhausted cells. The precise cues and mechanisms directing subset formation are incompletely understood. Here, we show that growth factor independent-1 (Gfi1) is dynamically regulated in exhausted CD8+ T cells. During chronic LCMV Clone 13 infection, a previously under-described Ly108+CX3CR1+ subset expresses low levels of Gfi1 while other established subsets have high expression. Ly108+CX3CR1+ cells possess distinct chromatin profiles and represent a transitory subset that develops to effector-like and terminally-exhausted cells, a process dependent on Gfi1. Similarly, Gfi1 in tumor-infiltrating CD8+ T cells is required for the formation of terminally differentiated cells and endogenous as well as anti-CTLA-induced anti-tumor responses. Taken together, Gfi1 is a key regulator of the subset formation of exhausted CD8+ T cells.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59784-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59784-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59784-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().