Cruz-Guilloty, FernandoPipkin, Matthew E.Djuretic, Ivana M.Levanon, DitsaLotem, JosephLichtenheld, Mathias G.Groner, YoramRao, Anjana2010-10-282009Cruz-Guilloty, Fernando, Matthew E. Pipkin, Ivana M. Djuretic, Ditsa Levanon, Joseph Lotem, Mathias G. Lichtenheld, Yoram Groner, and Anjana Rao. 2009. Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. The Journal of Experimental Medicine 206:51-59.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:4513850Activation 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 Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (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.en-USJournal Article2010-10-2810.1084/jem.20081242