Chung Il Yup, Dong Hui Fang, Zhang Xia, Hassanein Nahed M A, Howard O M Zack, Oppenheim Joost J, Chen Xin
Laboratory of Molecular Immunoregulation, Center for Cancer Research, Frederick, MD 21702-1201, USA.
Cell Immunol. 2004 Nov-Dec;232(1-2):57-63. doi: 10.1016/j.cellimm.2005.01.011.
Since we have previously shown that dexamethasone (Dex) enhances the proportion of murine Treg cells, we tested the effect of IL-7, a promoter of T cell survival, together with Dex on human CD4+CD25+ Treg cells in an in vitro setting. The results showed that IL-7 in concert with Dex markedly augmented the generation of CD4+CD25+ T cells. To discern the origin of the induced CD4+CD25+ T cells, MACS-purified CD4+CD25-, and CD4+CD25+ cells were cultured in the presence of Dex and/or IL-7 for 4 days. Although two thirds of CD4+CD25- T cells became CD4+CD25+ T cells, they had no suppressive activity. In contrast, the original CD4+CD25+ T cells maintained suppressive activity after Dex/IL-7 treatment, however, there was not a significant expansion in their cell number. Dex and IL-7 did not induce additional Treg cells, but additively induced the expression of the activation marker CD25 by CD4+CD25- T cells. This combination may provide a novel means of priming CD4 T cells to respond to IL-2 and may prove useful in up-regulation of normal immune responses in immune deficient diseases.
由于我们之前已经表明地塞米松(Dex)可提高小鼠调节性T细胞(Treg细胞)的比例,因此我们在体外实验中检测了白细胞介素-7(IL-7,一种T细胞存活促进因子)与Dex共同作用对人CD4+CD25+ Treg细胞的影响。结果显示,IL-7与Dex协同作用显著增加了CD4+CD25+ T细胞的生成。为了确定诱导产生的CD4+CD25+ T细胞的来源,将通过磁性激活细胞分选法(MACS)纯化的CD4+CD25-细胞和CD4+CD25+细胞在Dex和/或IL-7存在的情况下培养4天。虽然三分之二的CD4+CD25- T细胞变成了CD4+CD25+ T细胞,但它们没有抑制活性。相比之下,原始的CD4+CD25+ T细胞在Dex/IL-7处理后仍保持抑制活性,然而,其细胞数量没有显著增加。Dex和IL-7并未诱导产生额外的Treg细胞,但可协同诱导CD4+CD25- T细胞表达激活标志物CD25。这种组合可能提供一种启动CD4 T细胞对IL-2作出反应的新方法,并且可能在免疫缺陷疾病中上调正常免疫反应方面证明是有用的。