Maturation of human dendritic cells with Saccharomyces cerevisiae (yeast) reduces the number and function of regulatory T cells and enhances the ratio of antigen-specific effectors to regulatory T cells.
Maturation of human dendritic cells with Saccharomyces cerevisiae (yeast) reduces the number and function of regulatory T cells and enhances the ratio of antigen-specific effectors to regulatory T cells.
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DOI：
10.1016/j.vaccine.2011.04.101
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发表时间：
2011-07-12
期刊：
影响因子：
5.5
通讯作者：
Tsang, Kwong Y.
中科院分区：
文献类型：
--
作者：
Cereda, Vittore;Vergati, Matteo;Huen, Ngar-Yee;di Bari, Maria Giovanna;Jochems, Caroline;Intrivici, Chiara;Gulley, James L.;Apelian, David;Schlom, Jeffrey;Tsang, Kwong Y.
我们比较了酵母处理的树突状细胞（dc）和cd40l成熟的树突状细胞（dc）诱导效应细胞的效果，以及CD4+CD25+CD127−FoxP3+调节性T细胞（Tregs）的数量和功能。用酵母或CD40L处理树突状细胞，并与分离的自体CD4+ T细胞共培养。与CD4+ T细胞与CD40L处理的dc （CD40L共培养）共培养的CD4+CD25+CD127−T细胞相比，从CD4+ T细胞与酵母处理的dc（酵母共培养）共培养中分离的CD4+CD25+CD127−T细胞中分离的FoxP3表达较低，抑制功能较弱。此外，与CD40L共培养相比，酵母共培养显示CD4+CD25+活化T细胞与Tregs的比例增加，th1相关细胞因子（IL-2、TNF-α、IFN-γ）和IL-6的产生增加。此外，与使用cd40l成熟的dc作为apc相比，使用酵母处理的dc作为抗原提呈细胞（apc）与肿瘤抗原CEA孵育，可以增强CEA特异性CD4+ T细胞的增殖。这是首次报道酵母处理/成熟的人类dc在降低Treg频率和功能以及提高效应与Treg比率方面的作用。这些结果为使用酵母作为癌症疫苗载体提供了额外的理论依据。
We compared the effects of yeast-treated human dendritic cells (DCs) with CD40L-matured human DCs for the induction of effector cells and the number and functionality of CD4+CD25+CD127− FoxP3+ regulatory T cells (Tregs). DCs were treated with yeast or CD40L and cocultured with isolated autologous CD4+ T cells. CD4+CD25+CD127− T cells isolated from the coculture of CD4+ T cells plus yeast-treated DCs (yeast coculture) had a lower expression of FoxP3 and decreased suppressive function compared to CD4+CD25+CD127− T cells isolated from the coculture of CD4+ T cells plus CD40L-treated DCs (CD40L coculture). Also, compared to the CD40L coculture, the yeast coculture showed increases in the ratio of CD4+CD25+ activated T cells to Tregs and in the production of Th1-related cytokines (IL-2, TNF-α, IFN-γ) and IL-6. In addition, yeast-treated DCs used as antigen-presenting cells (APCs) incubated with the tumor antigen CEA enhanced the proliferation of CEA-specific CD4+ T cells compared to the use of CD40L-matured DCs used as APCs. This is the first study to report on the role of yeast-treated/matured human DCs in reducing Treg frequency and functionality and in enhancing effector to Treg ratios. These results provide an additional rationale for the use of yeast as a vector in cancer vaccines.
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DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
5.5
作者：
Haller, Aurelia A.;Lauer, Georg M.;Duke, Richard C.
通讯作者：
Duke, Richard C.
影响因子：
100.3
作者：
Huehn, Jochen;Polansky, Julia K.;Hamann, Alf
通讯作者：
Hamann, Alf
影响因子：
56.9
作者：
Pasare, C;Medzhitov, R
通讯作者：
Medzhitov, R
影响因子：
11.5
作者：
Gulley, James L.;Arlen, Philip M.;Schlom, Jeffrey
通讯作者：
Schlom, Jeffrey