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 language | English |
|---|---|
| Pages (from-to) | 51-59 |
| Number of pages | 9 |
| Journal | Journal of Experimental Medicine |
| Volume | 206 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 16 2009 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs. / Cruz-Guilloty, Fernando; Pipkin, Matthew E.; Djuretic, Ivana M.; Levanon, Ditsa; Lotem, Joseph; Lichtenheld, Mathias G; Groner, Yoram; Rao, Anjana.
In: Journal of Experimental Medicine, Vol. 206, No. 1, 16.01.2009, p. 51-59.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Runx3 and T-box proteins cooperate to establish the transcriptional program of effector CTLs
AU - Cruz-Guilloty, Fernando
AU - Pipkin, Matthew E.
AU - Djuretic, Ivana M.
AU - Levanon, Ditsa
AU - Lotem, Joseph
AU - Lichtenheld, Mathias G
AU - Groner, Yoram
AU - Rao, Anjana
PY - 2009/1/16
Y1 - 2009/1/16
N2 - 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.
AB - 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.
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U2 - 10.1084/jem.20081242
DO - 10.1084/jem.20081242
M3 - Article
C2 - 19139168
AN - SCOPUS:60549090859
VL - 206
SP - 51
EP - 59
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -