Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death
Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death
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DOI：
10.1002/eji.200324506
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发表时间：
2004-03-01
影响因子：
5.4
通讯作者：
Howard, DMZ
中科院分区：
文献类型：
--
作者：
Chen, X;Murakami, T;Howard, DMZ
为了评价免疫抑制糖皮质激素对CD4(+)CD25(+)T细胞的体内影响，我们将地塞米松(Dex)注射到BALB/c小鼠体内。地塞米松可使淋巴器官中的CD4(+)CD25(+)细胞比例和CD4(+)CD25(+)细胞/CD4(+)CD25(-)细胞的比例增加，尤其是胸腺。这与我们在体外观察到的CD4(+)CD25(+)T细胞表达更高水平的糖皮质激素受体和Bcl2有关，因此比CD4(+)CD25(-)T细胞更能抵抗地塞米松介导的细胞死亡。IL-2对地塞米松诱导的CD4(+)CD25(-)T细胞有选择性保护作用，而IL-7和IL-15对地塞米松诱导的CD25(-)T细胞无保护作用。地塞米松处理的CD4(+)CD25(+)T细胞表达细胞内CTLA-4和糖皮质激素诱导的肿瘤坏死因子受体的水平高于新鲜的CD4(+)CD25(+)T细胞，但对TCR刺激仍无反应，并抑制了CD4(+)CD25(-)T细胞的增殖。这些结果表明，地塞米松治疗除了抑制细胞因子转录外，还允许功能性的CD4(+)CD25(-)T调节细胞存活，这一特性可能与糖皮质激素的抗炎和免疫抑制作用有关。我们的数据还表明，选择性地保护CD4(+)CD25(+)T细胞免于凋亡可能在IL-2免疫耐受中起作用。
To evaluate the in vivo effect of immunosuppressive glucocorticoids on CD4(+)CD25(+) T regulatory cells, we injected dexamethasone (Dex) into BALB/c mice. Administration of Dex enhanced the proportion of CD4(+)CD25(+) cells and the ratio of CD4(+)CD25(+) cells to CD4(+)CD25(-) cells in the lymphoid organs, especially in the thymus. This correlates with our in vitro observation that CD4(+)CD25(+) T cells express higher levels of glucocorticoid receptor and Bcl-2, and are therefore more resistant to Dex-mediated cell death than CD4(+)CD25(-) T cells. Furthermore, IL-2 selectively protected CD4(+)CD25(-) T cells from Dex-induced cell death, while IL-7 and IL-15 did not exert preferential protective effects. Dex-treated CD4(+)CD25(+) T cells expressed higher levels of intracellular CTLA-4 and surface glucocorticoid-induced TNF receptor than fresh CD4(+)CD25(+) T cells, but still failed to respond to TCR stimulation and inhibited proliferation of CD4(+)CD25(-) T cells. These results suggest that, in addition to suppressing cytokine transcription, Dex treatment is permissive for the survival of functional CD4(+)CD25(-) T regulatory cells, and this property may contribute to the anti-inflammatory and immunosuppressive efficacy of glucocorticoids. Our data also suggest that selective protection of CD4(+)CD25(+) T cell from apoptosis may constitute a role in immune tolerance for IL-2.