The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells
Open accessAbstract
SUMMARY Interleukin(IL)-2 and inflammation regulate effector and memory cytolytic T-lymphocyte (CTL) generation during infection. We demonstrate a complex interplay between IL-2 and inflammatory signals during CTL differentiation. IL-2 stimulation induced the transcription factor eomesodermin (Eomes), upregulated perforin (Prf1) transcription, and repressed re-expression of memory CTL markers Bcl6 and IL-7Rα. Binding of Eomes and STAT5 to Prf1 cis-regulatory regions correlated with transcriptional initiation (increased recruitment of RNA polymerase II to the Prf1 promoter). Inflammation (CpG, IL-12) enhanced expression of IL-2Rα and the transcription factor T-bet, but countered late Eomes and perforin induction while preventing IL-7Rα repression by IL-2. After infection of mice with lymphocytic choriomeningitis virus, IL-2Rα-deficient effector CD8+ T cells expressed more Bcl6 but less perforin and granzyme B, formed fewer KLRG-1+ and T-bet-expressing CTL, and killed poorly. Thus, inflammation influences both effector and memory CTL differentiation, whereas persistent IL-2 stimulation promotes effector at the expense of memory CTL development.
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Joshi, N. S., Cui, W., Chandele, A., Lee, H. K., Urso, D. R., Hagman, J., Gapin, L., & Kaech, S. M. (2007) · Immunity · doi:10.1016/j.immuni.2007.07.010 · Cited by 1,861
Kaech, S. M., Tan, J. T., Wherry, E. J., Konieczny, B. T., Surh, C. D., & Ahmed, R. (2003) · Nature Immunology · doi:10.1038/ni1009 · Cited by 1,830 · cited 1×
“We examined IL-7Ra (CD127) regulation in more detail because effector cells that reinduce IL-7Ra at the peak of the response to some acute infections are enriched for cells that form long-lived memory CTL (Kaech et al., 2003).”
BackgroundMalek, T. R. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090357 · Cited by 1,079
Cited by
Transcriptional control of effector and memory CD8+ T cell differentiation
Kaech, S. M., & Cui, W. (2012) · Nature Reviews Immunology · doi:10.1038/nri3307 · Cited by 1,628
CD4+ T cell help in cancer immunology and immunotherapy
Borst, J., Ahrends, T., Bąbała, N., Melief, C. J. M., & Kastenmüller, W. (2018) · Nature Reviews Immunology · doi:10.1038/s41577-018-0044-0 · Cited by 1,585
Perforin and granzymes: function, dysfunction and human pathology
Voskoboinik, I., Whisstock, J. C., & Trapani, J. A. (2015) · Nature Reviews Immunology · doi:10.1038/nri3839 · Cited by 1,327
The Transcription Factor NFAT Promotes Exhaustion of Activated CD8 + T Cells
Martinez, G. J., Pereira, R. M., Äijö, T., Kim, E. Y., Marangoni, F., Pipkin, M. E., Togher, S., Heissmeyer, V., Zhang, Y. C., Crotty, S., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.01.006 · Cited by 857
“When differentiated into ‘‘memory’’ CTLs (Pipkin et al., 2010) and restimulated with PMA and ionomycin in vitro, NFAT1,2 double-deficient CD8+ T cells showed clearly decreased induction of the effector cytokines IL-2 and IFN-g compared toWT or singly NFAT1- or NFAT2-deficient CD8+ T cells (Figure 5A); they also showed…”
InfluentialSelf-citationThe who's who of T ‐cell differentiation: Human memory T ‐cell subsets
Mahnke, Y. D., Brodie, T. M., Sallusto, F., Roederer, M., & Lugli, E. (2013) · European Journal of Immunology · doi:10.1002/eji.201343751 · Cited by 817
Metadata
- Authors
- Pipkin, M. E., Sacks, J. A., Cruz-Guilloty, F., Lichtenheld, M. G., Bevan, M. J., & Rao, A.
- Venue
- Immunity
- Publisher
- Elsevier BV
- Published
- 2010-01
- Volume
- 32
- Issue
- 1
- Pages
- 79-90
- ISSN
- 1074-7613 (ISSN-L)
- OpenAlex
- W1990555844
- Cited by
- 795
- References
- 3
- FWCI
- 22.13
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Pipkin, M. E., Sacks, J. A., Cruz-Guilloty, F., Lichtenheld, M. G., Bevan, M. J., & Rao, A. (2010). Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells. Immunity. https://doi.org/10.1016/j.immuni.2009.11.012
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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