Control of Effector CD8 + T Cell Function by the Transcription Factor Eomesodermin
Abstract
Activated CD8 + T cells play a critical role in host defense against viruses, intracellular microbes, and tumors. It is not clear if a key regulatory transcription factor unites the effector functions of CD8 + T cells. We now show that Eomesodermin ( Eomes ), a paralogue of T-bet , is induced in effector CD8 + T cells in vitro and in vivo. Ectopic expression of Eomes was sufficient to invoke attributes of effector CD8 + T cells, including interferon-γ (IFN-γ), perforin, and granzyme B. Loss-of-function analysis suggests Eomes may also be necessary for full effector differentiation of CD8 + T cells. We suggest that Eomesodermin is likely to complement the actions of T-bet and act as a key regulatory gene in the development of cell-mediated immunity.
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In activated CD8 T cells, these TFs regulate production of cytokines and lytic proteins such as TNF, IFNγ, GzmB, and perforin.
“In activated CD8 T cells, these TFs regulate the production of cytokines and lytic proteins, such as tumor necrosis factor (TNF), IFNγ, granzyme B (GzmB), and perforin (48).”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [48]
Cytotoxic subset appeared dominantly regulated by TFs associated with cytotoxicity and TH1 polarization, including Eomes, Runx2, Runx3, and Tbx21 regulons.
“The cytotoxic subset appeared to be dominantly regulated by TFs associated with cytotoxicity and T helper 1 (TH1) polarization, including Eomes, Runx2, Runx3, and Tbx21 regulons [Fig. 5B; (42, 48)].”
From Aging promotes reorganization of the CD4 T cell landscape toward extreme regulatory and effector phenotypes (2019) · cites this paper as [48]
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- Authors
- Pearce, E. L., Mullen, A. C., Martins, G. A., Krawczyk, C. M., Hutchins, A. S., Zediak, V. P., Banica, M., DiCioccio, C. B., Gross, D. A., Mao, C.-A., Shen, H., Cereb, N., Yang, S. Y., Lindsten, T., Rossant, J., Hunter, C. A., & Reiner, S. L.
- Affiliations
- Mount Sinai Hospital (CA)
- Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
- Corresponding author
- Reiner, Steven L.
- ORCID
- Venue
- Science
- Published
- 2003-11-07
- Volume
- 302
- Issue
- 5647
- Pages
- 1041-1043
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2119319172
- Cited by
- 1,014
- References
- 18
- Citations by year
- 2026: 25 · 2025: 36 · 2024: 32 · 2023: 47 · 2022: 45 · 2021: 72 · 2020: 60 · 2019: 49 · 2018: 63 · 2017: 33 · 2016: 50 · 2015: 45 · 2014: 56 · 2013: 69 · 2012: 56
- FWCI
- 8.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (T32GM007229, GM-07229)
- National Institute of Allergy and Infectious Diseases (AI 042370, R01AI042370)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- Eomesodermin, CD8+ T cells, effector T cell differentiation, transcription factors, T-bet, interferon-gamma, perforin, granzyme B, cell-mediated immunity, transcriptional regulation
- MeSH terms
- T-bet Transcription Factor, Amino Acid Sequence, Animals, Arenaviridae Infections, Base Sequence, Cell Differentiation, Cytotoxicity, Immunologic, Gene Expression Regulation, Interferon-gamma, Lymphocyte Activation, Lymphocytic choriomeningitis virus, Membrane Glycoproteins, Mice, Inbred BALB C, Mice, Inbred C57BL, Molecular Sequence Data, RNA, Messenger, Serine Endopeptidases, Transcription Factors, CD8-Positive T-Lymphocytes, Th2 Cells, T-Box Domain Proteins, Mice, Pore Forming Cytotoxic Proteins, Granzymes, Perforin
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