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灵芝多糖作为 Th1 佐剂,在体内刺激细胞毒性 T 细胞应答。

Polysaccharides from Ganoderma formosanum function as a Th1 adjuvant and stimulate cytotoxic T cell response in vivo.

机构信息

Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan, ROC.

Graduate Institute of Immunology, National Taiwan University, College of Medicine, Taipei 100, Taiwan, ROC.

出版信息

Vaccine. 2014 Jan 9;32(3):401-8. doi: 10.1016/j.vaccine.2013.11.027. Epub 2013 Nov 17.

Abstract

The fungus of Ganoderma is a basidiomycete that possesses a variety of pharmacological effects and has been used in traditional Asian medicine for centuries. Ganoderma formosanum is a native Ganoderma species isolated in Taiwan, and we have previously demonstrated that PS-F2, a polysaccharide fraction purified from the submerged culture broth of G. formosanum, exhibits immunostimulatory properties in macrophages. In this study, we further characterized the adjuvant functions of PS-F2. In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40. PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II. In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes. When used as an adjuvant in vivo with the ovalbumin (OVA) antigen, PS-F2 stimulated OVA-specific antibody production and primed IFN-γ production in OVA-specific T lymphocytes. PS-F2-adjuvated immunization also induced OVA-specific CTLs, which protected mice from a challenge with tumor cells expressing OVA. Collectively, our data show that PS-F2 functions as an adjuvant capable of inducing a Th1-polarized adaptive immune response, which would be useful in vaccines against viruses and tumors.

摘要

灵芝真菌是一种担子菌,具有多种药理作用,几个世纪以来一直被用于亚洲传统医学。灵芝是一种原产于台湾的灵芝物种,我们之前已经证明,从灵芝液体培养物中纯化的多糖 PS-F2 在巨噬细胞中具有免疫刺激特性。在这项研究中,我们进一步表征了 PS-F2 的佐剂功能。在体外,PS-F2 刺激树突状细胞 (DC) 产生促炎细胞因子,包括 TNF-α、白细胞介素 (IL)-6 和 IL-12/IL-23 p40。PS-F2 还刺激 DC 表达成熟标志物 CD40、CD80、CD86 和 MHC 类 II。在小鼠脾细胞培养物中,PS-F2 处理导致 T 淋巴细胞中 T-bet 和干扰素 (IFN)-γ 的表达升高。当用作体内佐剂与卵清蛋白 (OVA) 抗原一起使用时,PS-F2 刺激 OVA 特异性抗体产生并在 OVA 特异性 T 淋巴细胞中引发 IFN-γ 产生。PS-F2 佐剂免疫还诱导了 OVA 特异性 CTL,可保护小鼠免受表达 OVA 的肿瘤细胞的攻击。总之,我们的数据表明 PS-F2 作为一种佐剂,能够诱导 Th1 极化的适应性免疫反应,这对于针对病毒和肿瘤的疫苗将非常有用。

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