Role of T-bet in Commitment of T H 1 Cells Before IL-12-Dependent Selection-Reference-Cited by-同舟云学术

Role of T-bet in Commitment of T H 1 Cells Before IL-12-Dependent Selection

Published:2001-06-08 Issue:5523 Volume:292 Page:1907-1910
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Mullen Alan C.¹,High Frances A.¹,Hutchins Anne S.¹,Lee Hubert W.¹,Villarino Alejandro V.¹,Livingston David M.²,Kung Andrew L.²,Cereb Nezih³,Yao Tso-Pang⁴,Yang Soo Y.³,Reiner Steven L.¹

Affiliation:

1. Abramson Family Cancer Research Institute and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104–6160, USA.

2. Dana Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.

3. Histogenetics, Inc., and Center for Genetic Polymorphism, Hawthorne, NY 10532, USA.

4. Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Abstract

How cytokines control differentiation of helper T (T H ) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies T H 1 effector fate by targeting chromatin remodeling to individual interferon-γ (IFN-γ) alleles and by inducing IL-12 receptor β2 expression. Subsequently, it appears that IL-12/STAT4 serves two essential functions in the development of T H 1 cells: as growth signal, inducing survival and cell division; and as trans-activator, prolonging IFN-γ synthesis through a genetic interaction with the coactivator, CREB-binding protein. These results suggest that a cytokine does not simply induce T H fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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