First Author | Cruz-Guilloty F | Year | 2009 |
Journal | J Exp Med | Volume | 206 |
Issue | 1 | Pages | 51-9 |
PubMed ID | 19139168 | Mgi Jnum | J:144022 |
Mgi Id | MGI:3829801 | Doi | 10.1084/jem.20081242 |
Citation | Cruz-Guilloty F, et al. (2009) Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. J Exp Med 206(1):51-9 |
abstractText | 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 Eomesodermin (Eomes), T-box transcription factors that regulate the early and late phases of interferon (IFN) gamma 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-gamma, 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. |