Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1
Summary: T-bet and FOXO1 are transcription factors canonically associated with effector and memory T cell fates, respectively. During an infectious response, these factors direct the development of CD8+ T cell fates, where T-bet deficiency leads to ablation of only short-lived effector cells, while...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723009221 |
| _version_ | 1797731084705726464 |
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| author | Daria L. Ivanova Scott B. Thompson Jared Klarquist Michael G. Harbell Augustus M. Kilgore Erika L. Lasda Jay R. Hesselberth Christopher A. Hunter Ross M. Kedl |
| author_facet | Daria L. Ivanova Scott B. Thompson Jared Klarquist Michael G. Harbell Augustus M. Kilgore Erika L. Lasda Jay R. Hesselberth Christopher A. Hunter Ross M. Kedl |
| author_sort | Daria L. Ivanova |
| collection | DOAJ |
| description | Summary: T-bet and FOXO1 are transcription factors canonically associated with effector and memory T cell fates, respectively. During an infectious response, these factors direct the development of CD8+ T cell fates, where T-bet deficiency leads to ablation of only short-lived effector cells, while FOXO1 deficiency results in selective loss of memory. In contrast, following adjuvanted subunit vaccination in mice, both effector- and memory-fated T cells are compromised in the absence of either T-bet or FOXO1. Thus, unlike responses to challenge with Listeria monocytogenes, productive CD8+ T cell responses to adjuvanted vaccination require coordinated regulation of FOXO1 and T-bet transcriptional programs. Single-cell RNA sequencing analysis confirms simultaneous T-bet, FOXO1, and TCF1 transcriptional activity in vaccine-elicited, but not infection-elicited, T cells undergoing clonal expansion. Collectively, our data show that subunit vaccine adjuvants elicit T cell responses dependent on transcription factors associated with effector and memory cell fates. |
| first_indexed | 2024-03-12T11:53:39Z |
| format | Article |
| id | doaj.art-5b185e3c9b34469baf940c2d2c73e409 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-03-12T11:53:39Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-5b185e3c9b34469baf940c2d2c73e4092023-08-31T05:02:10ZengElsevierCell Reports2211-12472023-08-01428112911Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1Daria L. Ivanova0Scott B. Thompson1Jared Klarquist2Michael G. Harbell3Augustus M. Kilgore4Erika L. Lasda5Jay R. Hesselberth6Christopher A. Hunter7Ross M. Kedl8Department of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Biochemistry & Molecular Genetics, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Biochemistry & Molecular Genetics, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USADepartment of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Immunology and Microbiology, University of Colorado – Anschutz Medical Campus, Aurora, CO 80045, USA; Corresponding authorSummary: T-bet and FOXO1 are transcription factors canonically associated with effector and memory T cell fates, respectively. During an infectious response, these factors direct the development of CD8+ T cell fates, where T-bet deficiency leads to ablation of only short-lived effector cells, while FOXO1 deficiency results in selective loss of memory. In contrast, following adjuvanted subunit vaccination in mice, both effector- and memory-fated T cells are compromised in the absence of either T-bet or FOXO1. Thus, unlike responses to challenge with Listeria monocytogenes, productive CD8+ T cell responses to adjuvanted vaccination require coordinated regulation of FOXO1 and T-bet transcriptional programs. Single-cell RNA sequencing analysis confirms simultaneous T-bet, FOXO1, and TCF1 transcriptional activity in vaccine-elicited, but not infection-elicited, T cells undergoing clonal expansion. Collectively, our data show that subunit vaccine adjuvants elicit T cell responses dependent on transcription factors associated with effector and memory cell fates.http://www.sciencedirect.com/science/article/pii/S2211124723009221CP: Immunology |
| spellingShingle | Daria L. Ivanova Scott B. Thompson Jared Klarquist Michael G. Harbell Augustus M. Kilgore Erika L. Lasda Jay R. Hesselberth Christopher A. Hunter Ross M. Kedl Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 Cell Reports CP: Immunology |
| title | Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 |
| title_full | Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 |
| title_fullStr | Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 |
| title_full_unstemmed | Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 |
| title_short | Vaccine adjuvant-elicited CD8+ T cell immunity is co-dependent on T-bet and FOXO1 |
| title_sort | vaccine adjuvant elicited cd8 t cell immunity is co dependent on t bet and foxo1 |
| topic | CP: Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723009221 |
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