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Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells

Open access
Pipkin, Matthew E., Sacks, Jilian A., Cruz-Guilloty, Fernando, Lichtenheld, Mathias G., Bevan, Michael J., Rao, Anjana·2010·Immunity

Abstract

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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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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CoChat. (2026). Citation check: Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells. https://app.cochat.ai/papers/10.1016/j.immuni.2009.11.012
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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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