In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 26 ( 2001-12-18), p. 15137-15142
Abstract:
Differentiation of naive CD4 + T cells into
IFN-γ-producing T helper 1 (T H 1) cells is pivotal
for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family,
has been reported to play a critical role in this process, promoting IFN-γ production. Although terminal T H 1 differentiation
occurs over days, we now show that challenge of mice with a prototypical T H 1-inducing stimulus, Toxoplasma
gondii soluble extract, rapidly induced IFN-γ and T-bet;
T-bet induction was substantially lower in IFN-γ-deficient mice. Naive T cells expressed little T-bet, but this transcription factor was
induced markedly by the combination of IFN-γ and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after
IFN-γ stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although
T-bet was induced rapidly and directly by IFN-γ, it was not induced by IFN-α, lipopolysaccharide, or IL-1, indicating that this action of
IFN-γ was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-γ gene
regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings
substantially alter the current view of T-bet in IFN-γ regulation and promotion of cell-mediated immune responses.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.261570598
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
2001
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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