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[Gd@C(82)(OH)(22)](n) 纳米颗粒诱导树突状细胞成熟并激活 Th1 免疫应答。

[Gd@C(82)(OH)(22)](n) nanoparticles induce dendritic cell maturation and activate Th1 immune responses.

机构信息

Tianjin Medical University, Research Center of Basic Medic Sciences, Cancer Institute and Hospital, Tianjin 300060, China.

出版信息

ACS Nano. 2010 Feb 23;4(2):1178-86. doi: 10.1021/nn901478z.

Abstract

Dendritic cells play a pivotal role in host immune defense, such as elimination of foreign pathogen and inhibition of tumorigenesis. In this paper, we report that Gd@C(82)(OH)(22) could induce phenotypic maturation of dendritic cells by stimulating DC production of cytokines including IL-12p70, upregulating DC co-stimulatory (CD80, CD83, and CD86) and MHC (HLA-A,B,C and HLA-DR) molecules, and switching DCs from a CCL5-responsive to a CCL19-responsive phenotype. We found that Gd@C(82)(OH)(22) can induce dendritic cells to become functionally mature as illustrated by their capacity to activate allogeneic T cells. Mice immunized with ovalbumin in the presence of Gd@C(82)(OH)(22) exhibit enhanced ovalbumin-specific Th1-polarized immune response as evidenced by the predominantly increased production of IFNgamma, IL-1beta, and IL-2. The Gd@C(82)(OH)(22) nanoparticle is a potent activator of dendritic cells and Th1 immune responses. These new findings also provide a rational understanding of the potent anticancer activities of Gd@C(82)(OH)(22) nanoparticles reported previously.

摘要

树突状细胞在宿主免疫防御中发挥着关键作用,如消除外来病原体和抑制肿瘤发生。在本文中,我们报告了 Gd@C(82)(OH)(22) 可以通过刺激树突状细胞产生细胞因子(包括 IL-12p70)、上调树突状细胞共刺激分子(CD80、CD83 和 CD86)和 MHC(HLA-A、B、C 和 HLA-DR)分子,将树突状细胞从 CCL5 反应型转变为 CCL19 反应型,从而诱导树突状细胞的表型成熟。我们发现 Gd@C(82)(OH)(22) 可以诱导树突状细胞成熟,表现为其激活同种异体 T 细胞的能力。在 Gd@C(82)(OH)(22) 的存在下用卵清蛋白免疫的小鼠表现出增强的卵清蛋白特异性 Th1 极化免疫反应,这表现在 IFNgamma、IL-1beta 和 IL-2 的产生主要增加。Gd@C(82)(OH)(22) 纳米颗粒是树突状细胞和 Th1 免疫反应的有效激活剂。这些新发现还为以前报道的 Gd@C(82)(OH)(22) 纳米颗粒的强大抗癌活性提供了合理的理解。

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