Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer
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 directi...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59784-1 |
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| author | Oluwagbemiga A. Ojo Hongxing Shen Jennifer T. Ingram James A. Bonner Robert S. Welner Georges Lacaud Allan J. Zajac Lewis Z. Shi |
| author_facet | Oluwagbemiga A. Ojo Hongxing Shen Jennifer T. Ingram James A. Bonner Robert S. Welner Georges Lacaud Allan J. Zajac Lewis Z. Shi |
| author_sort | Oluwagbemiga A. Ojo |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-3f8df2d032ae42daaa4dec401eee2d85 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-3f8df2d032ae42daaa4dec401eee2d852025-08-20T03:10:30ZengNature PortfolioNature Communications2041-17232025-05-0116111810.1038/s41467-025-59784-1Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancerOluwagbemiga A. Ojo0Hongxing Shen1Jennifer T. Ingram2James A. Bonner3Robert S. Welner4Georges Lacaud5Allan J. Zajac6Lewis Z. Shi7Department of Radiation Oncology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Radiation Oncology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Microbiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Radiation Oncology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Hematology & Oncology, Heersink School of Medicine, University of Alabama at BirminghamCancer Research UK Manchester Institute, The University of ManchesterDepartment of Microbiology, Heersink School of Medicine, University of Alabama at BirminghamDepartment of Radiation Oncology, Heersink School of Medicine, University of Alabama at BirminghamAbstract 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.https://doi.org/10.1038/s41467-025-59784-1 |
| spellingShingle | Oluwagbemiga A. Ojo Hongxing Shen Jennifer T. Ingram James A. Bonner Robert S. Welner Georges Lacaud Allan J. Zajac Lewis Z. Shi Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer Nature Communications |
| title | Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer |
| title_full | Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer |
| title_fullStr | Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer |
| title_full_unstemmed | Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer |
| title_short | Gfi1 controls the formation of effector-like CD8+ T cells during chronic infection and cancer |
| title_sort | gfi1 controls the formation of effector like cd8 t cells during chronic infection and cancer |
| url | https://doi.org/10.1038/s41467-025-59784-1 |
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