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Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription Factor
Open accessAbstract
As acute infections resolve, effector CD8(+) T cells differentiate into interleukin-7 receptor(lo) (IL-7R(lo)) short-lived effector cells (SLECs) and IL-7R(hi) memory precursor effector cells (MPECs) capable of generating long-lived memory CD8(+) T cells. By using another SLEC marker, KLRG1, we found that KLRG1(hi) effector cells began appearing early during infection and were committed to downregulating IL-7R. Unlike IL-7R(hi) MPECs, KLRG1(hi) IL-7R(lo) SLECs relied on IL-15, but IL-15 could not sustain their long-term maintenance or homeostatic turnover. The decision between SLEC and MPEC fates was regulated by the amount of inflammatory cytokines (i.e., IL-12) present during T cell priming. According to the amount of inflammation, a gradient of T-bet was created in which high T-bet expression induced SLECs and low expression promoted MPECs. These results elucidate a mechanism by which the innate immune system sets the relative amounts of a lineage-determining transcription factor in activated CD8(+) T cells and, correspondingly, regulates their memory cell potential.
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“Ag-specific CD8 T cells derived from the effector phase of a response can express various combinations of CD127 and KLRG1, which define either more short-lived effector cells (SLECs; CD127−KLRG1+), which are lost during the contraction phase of the immune response, or memory precursor effector cells (MPECs; CD127+KLRG1−), which are more likely to persist and contribute to memory populations [224,”
From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [225]
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Metadata
- Authors
- Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M.
- Affiliations
- Yale University (US)
- National Jewish Health (US)
- Corresponding author
- Kaech, Susan M.
- ORCID
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2007-08
- Volume
- 27
- Issue
- 2
- Pages
- 281-295
- ISSN
- 1074-7613 (ISSN-L)
- PMC
- PMC2034442
- OpenAlex
- W1985294654
- Cited by
- 1,861
- References
- 50
- Citations by year
- 2026: 77 · 2025: 99 · 2024: 94 · 2023: 112 · 2022: 108 · 2021: 137 · 2020: 125 · 2019: 105 · 2018: 99 · 2017: 73 · 2016: 105 · 2015: 110 · 2014: 106 · 2013: 117 · 2012: 102
- FWCI
- 25.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Immunity (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Wellcome Trust
- National Institute of Allergy and Infectious Diseases (P01AI022295, R01AI057485, R01AI054661, P01 AI22295, T32AI055403, R01AI056322, R01AI066232)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- CD8+ T cells, short-lived effector cells, memory precursor effector cells, T-bet, IL-7 receptor, KLRG1, IL-15, IL-12, inflammation, T cell differentiation, memory T cell generation, innate immune regulation
- MeSH terms
- T-bet Transcription Factor, Animals, Immunologic Memory, Infections, Inflammation, Interferon-gamma, Mice, Mutant Strains, Receptors, Immunologic, Biomarkers, Cytokines, CD8-Positive T-Lymphocytes, Interleukin-12, Interleukin-15, Receptors, Interleukin-7, T-Box Domain Proteins, Lectins, C-Type, Mice
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