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Updated: Jun 3, 2026
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
Published on: January 22, 2019
[Trichostatin A inhibits the activation of CD(4)(+) T cells by suppressing CD(28) expression in mice]
Qiang WEI1, Xiao-yun WEN, Chuan-fu DU
1Department of Organ Transplantation, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. weiqiang0915@163.com
Objective:
To investigate the mechanism of trichostatin A(TSA), a histone deacetylase (HDAC) inhibitor, in inhibiting the activation of CD(4)(+) T cells in mice.
Methods:
The CD(4)(+) T cells isolated from the spleen of C57BL mice were treated with different concentrations of TSA (2, 20, and 200 nmol/L) for 24 h, and CD(3), CD(28) and interleukin-2 (IL-2) mRNA levels were measured with reverse transcription-polymerase chain reaction. The protein expressions of CD(3), CD(28) and IL-2 were measured by fluorescence-activated cell sorting and ELISA analysis. ZAP70 and PI3K protein expression in CD(4)(+) T cells activated by CD(3) and CD(28) monoclonal antibody were analyzed by Western blotting.
Results:
TSA dose-dependently inhibited the transcription and protein expression of CD28 in CD(4)(+) T cells and reduced the expression of PI3K protein in activated CD(4)(+) T cells, without showing significant effect on the expression of ZAP70. TSA treatment of the cells also resulted in significantly decreased mRNA and protein expressions of IL-2 (P<0.01).
Conclusion:
TSA can regulate the immunological activity of CD(4)(+) T cells by inducing mRNA and protein expressions of CD(28), which inhibits the activation of the co-stimulatory signal transduction in CD(4)(+) T cells and decreases the secretion of IL-2.
Insights
Trichostatin A (TSA), a histone deacetylase inhibitor, was found to inhibit CD4(+) T cell activation in mice. TSA reduces CD28 and IL-2 expression, impacting T cell immune responses.
Area of Science:
- Immunology
- Molecular Biology
- Pharmacology
Background:
- Histone deacetylase (HDAC) inhibitors, such as trichostatin A (TSA), are known to modulate gene expression.
- CD4(+) T cells play a critical role in adaptive immunity.
- Understanding the mechanisms by which HDAC inhibitors affect T cell activation is crucial for developing immunomodulatory therapies.
Purpose of the Study:
- To elucidate the mechanism by which trichostatin A (TSA) inhibits the activation of CD4(+) T cells in a mouse model.
- To investigate the effects of TSA on key signaling molecules and cytokines involved in T cell activation.
Main Methods:
- CD4(+) T cells were isolated from C57BL mice spleen and treated with varying concentrations of TSA.
- Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure mRNA levels of CD3, CD28, and IL-2.
- Protein expression of CD3, CD28, IL-2, ZAP70, and PI3K was analyzed using fluorescence-activated cell sorting (FACS), ELISA, and Western blotting.
Main Results:
- TSA demonstrated a dose-dependent inhibition of CD28 transcription and protein expression in CD4(+) T cells.
- TSA treatment led to reduced PI3K protein expression in activated CD4(+) T cells.
- A significant decrease in both mRNA and protein levels of IL-2 was observed following TSA treatment (P<0.01).
- TSA did not significantly affect ZAP70 expression.
Conclusions:
- TSA regulates CD4(+) T cell immunological activity by modulating CD28 expression.
- TSA inhibits T cell activation by interfering with co-stimulatory signal transduction pathways.
- The observed decrease in IL-2 secretion suggests TSA's potential as an immunosuppressive agent.
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