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

Journal Article (Journal Article)

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-gamma (IFN-gamma) alleles and by inducing IL-12 receptor beta2 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-gamma 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.

Full Text

Duke Authors

Cited Authors

  • Mullen, AC; High, FA; Hutchins, AS; Lee, HW; Villarino, AV; Livingston, DM; Kung, AL; Cereb, N; Yao, TP; Yang, SY; Reiner, SL

Published Date

  • June 8, 2001

Published In

Volume / Issue

  • 292 / 5523

Start / End Page

  • 1907 - 1910

PubMed ID

  • 11397944

International Standard Serial Number (ISSN)

  • 0036-8075

Digital Object Identifier (DOI)

  • 10.1126/science.1059835


  • eng

Conference Location

  • United States