The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans
The CD70-CD27 interaction during the stimulation with dendritic cells promotes naive CD4+ T cells to develop into T cells producing a broad array of immunostimulatory cytokines in humans
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DOI：
10.1093/intimm/dxp056
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发表时间：
2009-08-01
影响因子：
4.4
通讯作者：
Uchiyama, Takashi
中科院分区：
文献类型：
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作者：
Hashimoto-Okada, Mutsumi;Kitawaki, Toshio;Uchiyama, Takashi
在树突状细胞（dc）上表达的CD70已被证明在诱导小鼠有效的CD8(+) T细胞反应和T(h)1反应中起关键作用。然而，尚未广泛研究人类原代dc是否表达CD70，以及CD70- cd27相互作用是否促进原始CD4(+) T细胞在人类DC-T细胞相互作用中获得产生效应细胞因子的能力。在这里，我们发现人髓样树突状细胞（mDCs）和浆细胞样树突状细胞在CD40配体和促炎细胞因子或toll样受体配体的刺激下表达CD70。胸腺基质淋巴生成素和前列腺素E-2也能诱导CD70作用于mDCs。初始CD4(+) T细胞受dc刺激而非抗cd3 /CD28微珠刺激表达CD70。CD70和抗cd3 /CD28微珠刺激赋予了初始CD4(+) T细胞产生T(h)1 （ifn - γ）、T(h)2 （IL-4、IL-5、IL-13）细胞因子、IL-2和肿瘤坏死因子- α的能力。ifn - γ的产生与T-bet的诱导有关。用mDCs刺激的初始CD4(+) T细胞获得了以cd70依赖的方式产生广泛的免疫刺激细胞因子的增强能力。这些数据表明，在mDCs和活化的T细胞上表达的人类CD70向初始CD4(+) T细胞传递“基础水平”信号，而不是“极化”信号，其中CD70促进CD4(+) T细胞的发育，产生各种效应细胞因子，包括T(h)1和T(h)2类型，从而有助于增强广泛的免疫反应。
CD70 expressed on dendritic cells (DCs) has been shown to play a critical role in inducing effective CD8(+) T cell responses and a T(h)1 response in mice. However, it has not been extensively examined whether human primary DCs express CD70 and whether the CD70-CD27 interaction promotes naive CD4(+) T cells to acquire the ability to produce effector cytokines during the DC-T cell interaction in humans. Here, we show that human myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells stimulated with CD40 ligand together with pro-inflammatory cytokines or Toll-like receptor ligands express CD70. Thymic stromal lymphopoietin plus prostaglandin E-2 also induced CD70 on mDCs. Naive CD4(+) T cells stimulated with DCs but not with anti-CD3/CD28 microbeads expressed CD70. Stimulation with CD70 together with anti-CD3/CD28 microbeads imparted the ability to produce T(h)1 (IFN-gamma), T(h)2 (IL-4, IL-5, IL-13) cytokines, IL-2 and tumor necrosis factor-alpha to naive CD4(+) T cells. The production of IFN-gamma was associated with the induction of T-bet. Naive CD4(+) T cells stimulated with mDCs acquired an enhanced ability to produce a broad array of immunostimulatory cytokines in a CD70-dependent manner. These data suggest that human CD70 expressed on mDCs and activated T cells transmits a 'basal level' signal, rather than a 'polarizing' signal, to naive CD4(+) T cells, in that CD70 promotes the development of CD4(+) T cells that produce a variety of effector cytokines including both T(h)1 and T(h)2 types, thus contributing to the enhancement of a broad spectrum of immune responses.