Human Dendritic Cells Produce TGF-β1 under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells
Human Dendritic Cells Produce TGF-β1 under the Influence of Lung Carcinoma Cells and Prime the Differentiation of CD4+CD25+Foxp3+ Regulatory T Cells
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DOI：
10.4049/jimmunol.0712671
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发表时间：
2009-03-01
影响因子：
4.4
通讯作者：
Gregory, Christopher D.
中科院分区：
文献类型：
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作者：
Dumitriu, Ingrid E.;Dunbar, Donald R.;Gregory, Christopher D.
树突状细胞（Dendritic cells，DC）在包括抗肿瘤免疫在内的适应性免疫应答的发展中具有中心作用。肿瘤环境中存在的因子可以改变DC的成熟并抑制其活化T细胞的能力。使用基因表达分析，我们发现，人树突状细胞增加TGF-β 1的表达。用人肺癌细胞（LCC）培养后的转录物。与未暴露于肿瘤细胞的DC相比，这些DC产生增加量的TGF-β 1蛋白。LCCs还可降低未成熟DC的CD 86和HLA-DR表达。此外，LCC降低了成熟DC的CD 86表达和TNF-α和IL-12 p70的产生。此外，LCC还将成熟DC转化为产生TGF-β 1的细胞。这些产生TGF-β 1的DC在诱导幼稚CD 4（+）T细胞活化和维持其增殖和分化为Th 1（IFN-γ（+））效应细胞方面表现不佳。相反，产生TGF-β 1的DC表现出产生抑制T淋巴细胞增殖的CD 4（+）CD 25（+）Foxp 3（+）调节性T细胞的能力增加。这些结果确定了一种新的机制，通过这种机制，肿瘤细胞改变了人DC的功能，并有助于逃避免疫应答。免疫学杂志，2009，182：2795-2807.
Dendritic cells (DCs) have a central role in the development of adaptive immune responses, including antitumor immunity. Factors present in the tumor milieu can alter the maturation of DCs and inhibit their capacity to activate T cells. Using gene expression analysis, we found that human DCs increased the expression of TGF-beta 1. transcripts following culture with human lung carcinoma cells (LCCs). These DCs produced increased amounts of TGF-beta 1 protein compared with DCs not exposed to tumor cells. LCCs also decreased the expression or CD86 and HLA-DR by immature DCs. Furthermore, LCCs decreased CD86 expression and the production of TNF-alpha and IL-12 p70 by mature DCs. Moreover, LCCs also converted mature DCs into cells producing TGF-beta 1. These TGF-beta 1-producing DCs were poor at eliciting the activation of naive CD4(+) T cells and sustaining their proliferation and differentiation into Th1 (IFN-gamma(+)) effectors. Instead, TGF-beta 1 -producing DCs demonstrated an increased ability to generate CD4(+)CD25(+)Foxp3(+) regulatory T cells that suppress the proliferation of T lymphocytes. These results identify a novel mechanism by which the function of human DCs is altered by tumor cells and contributes to the evasion of the immune response. The Journal of Immunology, 2009, 182: 2795-2807.