Tianjin Medical University, Research Center of Basic Medic Sciences, Cancer Institute and Hospital, Tianjin 300060, China.
ACS Nano. 2010 Feb 23;4(2):1178-86. doi: 10.1021/nn901478z.
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.
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。
