Role of T-bet in commitment of TH1 cells before IL- 12-dependent selection

A. C. Mullen, F. A. High, A. S. Hutchins, H. W. Lee, A. V. Villarino, D. M. Livingston, A. L. Kung, N. Cereb, T. P. Yao, S. Y. Yang, S. L. Reiner

Research output: Contribution to journalArticlepeer-review

668 Scopus citations

Abstract

How cytokines control differentiation of helper T (TH) cells is controversial. We show that T-bet, without apparent assistance from interleukin 12 (IL-12)/STAT4, specifies TH1 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 TH1 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 TH fate choice but instead may act as an essential secondary stimulus that mediates selective survival of a lineage.

Original languageEnglish (US)
Pages (from-to)1907-1910
Number of pages4
JournalScience
Volume292
Issue number5523
DOIs
StatePublished - Jun 8 2001
Externally publishedYes

ASJC Scopus subject areas

  • General

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