Phenotypic Alterations of Dendritic Cells Are Involved in Suppressive Activity of Trichosanthin-Induced CD8+CD28− Regulatory T Cells
Phenotypic Alterations of Dendritic Cells Are Involved in Suppressive Activity of Trichosanthin-Induced CD8+CD28− Regulatory T Cells
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DOI：
10.4049/jimmunol.0901488
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发表时间：
2010-07
期刊：
影响因子：
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通讯作者：
Baolong Wang;Z. Jiao;Xiao-yi Shao;Liming Lu;N. Yang;Xiaorong Zhou;L. Xin;Yun Zhou;K. Chou
中科院分区：
文献类型：
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作者：
Baolong Wang;Z. Jiao;Xiao-yi Shao;Liming Lu;N. Yang;Xiaorong Zhou;L. Xin;Yun Zhou;K. Chou
调节性CD 8 + CD 28 − T细胞的性质和分化知之甚少。在这项研究中，我们证明了天然的天花粉蛋白（Tk），一种从中草药中分离的高度纯化的线性肽，能够通过激活分泌IL-4/IL-10的CD 8 + CD 28 −调节性T细胞（Tk）在低浓度下诱导对OVA特异性淋巴细胞增殖的强烈抑制。为了阐明其潜在机制，我们首先鉴定了两种类型的小鼠近交系，高敏感性（HS）和低敏感性，TK相关的抑制。它们分别是H-2d（或H-2b）和H-2k。只有当骨髓来源的树突状细胞（BDC）而不是纯化的T细胞用Tk处理时，才能诱发抑制，Tk与OVA特异性T-BDC相互作用。此外，在HS C57 BL/6小鼠中观察到了抑制OVA特异性T细胞增殖期间细胞因子/转录因子（IL-4+IL-10+IFN-γ− Gata 3 +T-bet−）的特殊模式，但在低易感性C3 H/He小鼠中没有观察到。同样，在存在Tk的情况下，CD 8 + CD 28 − Tk的百分比优先从5.5%扩增至26.1%，这种情况也仅在HS C57 BL/6小鼠中检测到。这些扩增的Tk能够诱导对单向MLCs的强烈抑制，这表明Tk诱导的低反应和CD 8 + CD 28 − Tk的激活可能受到不同遗传背景的影响。此外，在Tk刺激后，BDC的表型参数也发生了明显的变化，包括IL-10的产生增加，IL-12的分泌减少，以及检测到BDC上的Notch配体Jagged 1。总的来说，我们的数据表明，APC相关因子的变化是必不可少的，至少部分是TK诱导的CD 8 + CD 28 − T细胞的活化和分化。
The nature and differentiation of regulatory CD8+CD28− T cells are poorly understood. In this study, we demonstrate that native Ag trichosanthin (Tk), a highly purified linear peptide isolated from a Chinese medicinal herb, is able to induce strong suppression of OVA-specific lymphoproliferation at low concentrations via activation of IL-4/IL-10–secreting CD8+CD28− regulatory T cells (Tregs). To elucidate the underlying mechanisms, we firstly identified two types of mouse inbred strains, high susceptible (HS) and low susceptible, for the Tk-related suppression. They are H-2d (or H-2b) and H-2k, respectively. The suppression is evoked only if bone marrow-derived dendritic cells (BDCs) instead of purified T cells are treated with Tk in an OVA-specific T-BDC interaction. Moreover, a special pattern of cytokine/transcription factors (IL-4+IL-10+IFN-γ−Gata3+T-bet−) during suppressed OVA-specific T cell proliferation was observed in HS C57BL/6 but not in low-susceptible C3H/He mice. Consistently, the percentage of CD8+CD28− Tregs preferentially expanded from 5.5 to 26.1% in the presence of Tk, an occurrence that was also detected only in HS C57BL/6 mice. These expanded Tregs were able to induce a strong inhibition of one-way MLCs, which indicated that the Tk-induced hyporeaction and the activation of CD8+CD28− Tregs might be under the influence of different genetic backgrounds. Additionally, obvious alterations of phenotypic parameters of BDCs after Tk stimulation were also identified, including enhanced production of IL-10, decreased secretion of IL-12, and detection of Jagged1, a Notch ligand on BDCs. Collectively, our data suggest that the changed APC-related factors are essential, at least in part, for the activation and differentiation of Tk-induced CD8+CD28− Tregs.