Role of T-bet in commitment of TH1 cells before IL-12-dependent selection - PubMed (original) (raw)

. 2001 Jun 8;292(5523):1907-10.

doi: 10.1126/science.1059835.

Affiliations

• PMID: 11397944
• DOI: 10.1126/science.1059835

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

A C Mullen et al. Science. 2001.

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-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.

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