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

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

Research output: Contribution to journalArticle

390 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)79-90
Number of pages12
JournalImmunity
Volume32
Issue number1
DOIs
StatePublished - Jan 29 2010

Fingerprint

Interleukin-2
Interleukins
Inflammation
T-Lymphocytes
Perforin
Lymphocytic choriomeningitis virus
RNA Polymerase II
Nucleic Acid Regulatory Sequences
Interleukin-12
Transcription Factors
Infection

Keywords

  • CELLIMMUNO
  • MOLIMMUNO

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells. / Pipkin, Matthew E.; Sacks, Jilian A.; Cruz-Guilloty, Fernando; Lichtenheld, Mathias G; Bevan, Michael J.; Rao, Anjana.

In: Immunity, Vol. 32, No. 1, 29.01.2010, p. 79-90.

Research output: Contribution to journalArticle

Pipkin, Matthew E. ; Sacks, Jilian A. ; Cruz-Guilloty, Fernando ; Lichtenheld, Mathias G ; Bevan, Michael J. ; Rao, Anjana. / Interleukin-2 and Inflammation Induce Distinct Transcriptional Programs that Promote the Differentiation of Effector Cytolytic T Cells. In: Immunity. 2010 ; Vol. 32, No. 1. pp. 79-90.
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