Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs

Fernando Cruz-Guilloty, Matthew E. Pipkin, Ivana M. Djuretic, Ditsa Levanon, Joseph Lotem, Mathias G. Lichtenheld, Yoram Groner, Anjana Rao

Research output: Contribution to journalArticle

257 Scopus citations

Abstract

Activation of naive CD8 + T cells with antigen induces their differentiation into effector cytolytic T lymphocytes (CTLs). CTLs lyse infected or aberrant target cells by exocytosis of lytic granules containing the pore-forming protein perforin and a family of proteases termed granzymes. We show that effector CTL differentiation occurs in two sequential phases in vitro, characterized by early induction of T-bet and late induction of Eomesoder- min (Eomes), T-box transcription factors that regulate the early and late phases of inter- feron (IFN) γ expression, respectively. In addition, we demonstrate a critical role for the transcription factor Runx3 in CTL differentiation. Runx3 regulates Eomes expression as well as expression of three cardinal markers of the effector CTL program: IFN-γ, perforin, and granzyme B. Our data point to the existence of an elaborate transcriptional network in which Runx3 initially induces and then cooperates with T-box transcription factors to regulate gene transcription in differentiating CTLs.

Original languageEnglish (US)
Pages (from-to)51-59
Number of pages9
JournalJournal of Experimental Medicine
Volume206
Issue number1
DOIs
StatePublished - Jan 16 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Cruz-Guilloty, F., Pipkin, M. E., Djuretic, I. M., Levanon, D., Lotem, J., Lichtenheld, M. G., Groner, Y., & Rao, A. (2009). Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. Journal of Experimental Medicine, 206(1), 51-59. https://doi.org/10.1084/jem.20081242