Influence of histone deacetylase inhibitor romidepsin on phenotype and function of T lymphocytes in vitro |
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| Authors: | TIAN Xiao-jun XU Jing JIANG Ji-pin |
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| Institution: | 1. Intensive Care Unit, The Second Hospital of Jingzhou, Jingzhou 434000, China;
2. Operation Room, Tongji Hospital, Tongji Medical College, Huazhong University of Technology & Science, Wuhan 430030, China;
3. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Technology & Science, Wuhan 430030, China |
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| Abstract: | AIM: To explore the effects of romidepsin (FK228), a novel histone deacetylase inhibitor, on the effector and regulatory T cells in vitro.METHODS: As the reactive cells, lymphocytes, CD4+ T cells and CD8+ T cells were labelled with CFSE, and stimulated with anti-CD3 and anti-CD28 mAbs in the presence and absence of different levels of romidepsin (experimental group and positive control group), or PBS (placebo group).After 72 h, the proliferation of the cells was detected in different groups. The lymphocytes were stimulated with anti-CD3 and anti-CD28 mAbs in the presence and absence of different levels of romidepsin (experimental group and positive control group),or PBS (placebo group). After 72 h, the percentage of CD4+ Foxp3+ T cells and the levels of related cytokines were detected in different groups. RESULTS: The proliferation of CFSE-labelled lymphocytes, CD4+ T cells and CD8+ T cells triggered by anti-CD3 and anti-CD28 mAbs all were inhibited when cultured with romidepsin at concentrations of 1 μmol/L, 3 μmol/L and 5 μmol/L in a dose-dependent manner (P<0.05). Compared with placebo group, in the presence of anti-CD3 and anti-CD28 mAbs, 1 μmol/L romidepsin did not increase the percentage of CD4+ Foxp3+ T cells (P>0.05). When cultured with romidepsin at concentrations of 3 μmol/L and 5 μmol/L, the percentage of CD4+ Foxp3+ T cells was enhanced markedly (P<0.05). The levels of IL-10 and TNF-α in the supernatant were markedly increased in positive control group and 3 experimental groups (P<0.05), and the levels of cytokines in different experimental groups were gradually decreased with the elevation of FK228 concentration (P<0.05). The level of TGF-β was slightly increased in positive control group with no significant difference compared with placebo group (P>0.05). With the increase in the concentration of FK228 in different experimental groups, the TGF-β level was increased in a dose-dependent manner and there were significant differences in the 3 experimental groups. Meanwhile, significant differences existed between experimental groups and placebo group and between experimental groups and positive control group (P<0.05). CONCLUSION: Romidepsin inhibits the proliferation of CD4+ and CD8+ effector T cells and increases the percentage of CD4+ Foxp3+ regulatory T cells. It may be related to the increased level of TGF-β, but independent of IL-10. |
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| Keywords: | Histone deacetylase Romidepsin Regulatory T cells |
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