title: A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
abstract: To develop into committed T helper type 1 (Th1) cells, naive CD4(+) T cells not only need to acquire the capacity to produce interferon-gamma (IFN-gamma), but they also need to gain the ability to silence their interleukin-4 (IL-4) -producing potential. How Th1 cells silence their Th2 cytokine-producing potential is an important yet unresolved issue in Th1 immunity. We found that a lack of IL-4 stimulation was not sufficient to silence the IL-4-producing potential in activated CD4(+) T cells and that Th1-promoting factor was required. Although it has been shown that T-bet is a crucial factor in suppressing Il4 gene expression, it is unclear whether a continuous presence of T-bet is required to silence the Il4 gene in Th1 cells. To address this problem, we used an inducible form of T-bet - a T-bet-oestrogen receptor fusion molecule (T-bet-ER). We found that the activation of T-bet during primary or secondary culture was sufficient to silence IL-4-producing potential. On the other hand, the inactivation of T-bet after naïve CD4(+) T cells had differentiated into Th1 cells resulted in derepression of Il4 gene transcription. Additionally, we found that T-bet is required to maintain Ifng expression. Our data demonstrate that the continuous expression of T-bet is required for Th1 cells to silence their IL-4-producing potential.
authors.affiliation: Division of Allergy and Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Zan
authors.initials: Z
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Nishida
authors.forename: Melissa
authors.initials: M
authors.lastname: Brown
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Hua
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007108:Immune Tolerance; D015847:Interleukin-4 / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology; D020825:T-Box Domain Proteins / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D000098815:T-bet Transcription Factor
chemical_list: D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015847:Interleukin-4
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