Wang Yang, Cao Yan, Meng Yiming, You Zhenyu, Liu Xiaowei, Liu Zhihong
Department of Emergency, No. 1 Affiliated Hospital, China Medical University, No. 155, North Nanjing Street, Shenyang 110001, China.
Department of Immunology, School of Basic Medical Science, China Medical University, No. 92, North Second Road, Heping District, Shenyang 110001, China.
Int Immunopharmacol. 2014 Aug;21(2):255-60. doi: 10.1016/j.intimp.2014.05.011. Epub 2014 May 23.
Thymopentin is an immune-modulating peptide that can stimulate cellular immune responses and has been used in many immune handicapped cases [1]. However, despite documented reports proving its efficacy in immunoregulation, there have been no reports, as yet, concerning its impact on the maturation and function of dendritic cells (DCs). In this study, we analyzed the effects of thymopentin on the detailed regulation of maturation of murine bone-marrow-derived DCs (BMDCs). The phenotypic and structural maturation of BMDCs was confirmed by transmission electron microscopy (TEM) and flow cytometry (FCM). The functional maturation was confirmed by an acid phosphatase (ACP) activity test, FITC-dextran bio-assay, test of 5,6-carboxyfluorescein diacetate succinimidyl ester (CFSE), labeled CD4(+)T cell proliferation and enzyme-linked immunosorbent assay (ELISA). We determined that thymopentin up-regulated the expression of CD40, CD80, CD86, CD83, and MHC II molecules on BMDCs, down-regulated phagocytosis of BMDCs, increased BMDCs driven CD4(+)T cell proliferation, and enhanced BMDC production of IL-12 and TNF-α. Therefore, we concluded that thymopentin highly induces BMDC maturation and intensifies DC/T-cell pathways. These data also provide direct evidence and rationale concerning the potential clinical use of thymopentin in various immune handicapped cases and suggest that thymopentin should be considered as a potent adjuvant for DC-based vaccines.
胸腺五肽是一种免疫调节肽,可刺激细胞免疫反应,已用于多种免疫功能缺陷的病例[1]。然而,尽管有文献报道证明其在免疫调节方面的功效,但迄今为止,尚无关于其对树突状细胞(DCs)成熟和功能影响的报道。在本研究中,我们分析了胸腺五肽对小鼠骨髓来源的DCs(BMDCs)成熟的详细调节作用。通过透射电子显微镜(TEM)和流式细胞术(FCM)确认了BMDCs的表型和结构成熟。通过酸性磷酸酶(ACP)活性测试、FITC-葡聚糖生物测定、5,6-羧基荧光素二乙酸琥珀酰亚胺酯(CFSE)测试、标记的CD4(+)T细胞增殖和酶联免疫吸附测定(ELISA)确认了功能成熟。我们确定胸腺五肽上调了BMDCs上CD40、CD80、CD86、CD83和MHC II分子的表达,下调了BMDCs的吞噬作用,增加了BMDCs驱动的CD4(+)T细胞增殖,并增强了BMDCs产生IL-12和TNF-α的能力。因此,我们得出结论,胸腺五肽高度诱导BMDC成熟并强化DC/T细胞途径。这些数据也为胸腺五肽在各种免疫功能缺陷病例中的潜在临床应用提供了直接证据和理论依据,并表明胸腺五肽应被视为基于DC的疫苗的有效佐剂。