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- Title
A continuous T-bet expression is required to silence the interleukin-4-producing potential in T helper type 1 cells.
- Authors
Yonghua Zhuang; Zan Huang; Jun Nishida; Brown, Melissa; Lin Zhang; Hua Huang
- 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-γ (IFN-γ), 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.
- Publication
Immunology, 2009, Vol 128, Issue 1, p34
- ISSN
0019-2805
- Publication type
Academic Journal
- DOI
10.1111/j.1365-2567.2009.03049.x