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免疫刺激性CpG寡核苷酸和抗CD40抗体增强B淋巴瘤细胞的抗原呈递能力

Enhancement of antigen-presenting ability of B lymphoma cells by immunostimulatory CpG-oligonucleotides and anti-CD40 antibody.

作者信息

Chen W, Yu Y, Shao C, Zhang M, Wang W, Zhang L, Cao X

机构信息

Institute of Immunology, Zhejiang University, Hangzhou 310031, Zhejiang, People's Republic of China.

出版信息

Immunol Lett. 2001 May 1;77(1):17-23. doi: 10.1016/s0165-2478(01)00189-4.

Abstract

Immunostimulatory oligodeoxynucleotides containing the CpG motifs (CpG-ODN) can activate antigen-presenting cells including dendritic cells, macrophages, B cells, and enhance production of Thl cytokines. So, CpG-ODN has been regarded as a promising immune adjuvant. Using the A20 B lymphoma cell model, we investigated the effect of CpG-ODN on the immunogenicity of B lymphoma cells and whether CpG-ODN could enhance the antigen-presenting ability of B lymphoma cells. After incubation with CpG-ODN, proliferation of A20 cells remained unchanged. But CpG-ODN stimulation up-regulated the expression of MHC-I, MHC-II, CD40, ICAM-1 molecules in A20 cells, enhanced the antigen uptake ability of A20 cells, and promoted A20 cell production of IgM and IgG. More importantly, A20 cells activated by CpG-ODN could stimulate allogeneic T cells in MLR and antigen-primed T cells to proliferate more efficiently, suggesting the antigen-presenting ability of A20 B lymphoma cells could be enhanced by CpG-ODN stimulation and CpG-ODN-activated B lymphoma cells might be used as a potent cellular vaccine. Although anti-CD40 mAb was as effective as CpG-ODN at activating A20 cells and A20 cells expressed more CD40 molecules after CpG-ODN stimulation, a combination of CpG-ODN and anti-CD40 mAb had no synergistic effect on A20 cell activation. Our data expanded the potential application of CpG-ODN as an immunotherapeutic agent in cancer treatment.

摘要

含有CpG基序的免疫刺激寡脱氧核苷酸(CpG-ODN)可激活包括树突状细胞、巨噬细胞、B细胞在内的抗原呈递细胞,并增强Th1细胞因子的产生。因此,CpG-ODN被视为一种有前景的免疫佐剂。利用A20 B淋巴瘤细胞模型,我们研究了CpG-ODN对B淋巴瘤细胞免疫原性的影响以及CpG-ODN是否能增强B淋巴瘤细胞的抗原呈递能力。用CpG-ODN孵育后,A20细胞的增殖保持不变。但CpG-ODN刺激上调了A20细胞中MHC-I、MHC-II、CD40、ICAM-1分子的表达,增强了A20细胞的抗原摄取能力,并促进A20细胞产生IgM和IgG。更重要的是,经CpG-ODN激活的A20细胞能在混合淋巴细胞反应中更有效地刺激同种异体T细胞和抗原致敏的T细胞增殖,这表明CpG-ODN刺激可增强A20 B淋巴瘤细胞的抗原呈递能力,且CpG-ODN激活的B淋巴瘤细胞可能用作有效的细胞疫苗。尽管抗CD40单克隆抗体在激活A20细胞方面与CpG-ODN一样有效,且CpG-ODN刺激后A20细胞表达更多的CD40分子,但CpG-ODN与抗CD40单克隆抗体联合使用对A20细胞激活没有协同作用。我们的数据扩展了CpG-ODN作为免疫治疗剂在癌症治疗中的潜在应用。

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