Berberine(BBR)as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities.However,it is unknown if BBR can be applied ...Berberine(BBR)as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities.However,it is unknown if BBR can be applied without abrogating the efforts of vaccination.Here we show that priming of CD8^(+)T cells in the presence of BBR lead to improved central memory formation(Tcm)with substantially reduced effector proliferation,primarily orchestrated through activation of AMPK and Stat5.Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naIve recipients.Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy,suggesting appreciable benefits from using BBR in vaccination.Thus,our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.展开更多
记忆T细胞(memory T cell,Tm)作为人体免疫系统中的一个组成部分,在免疫应答中发挥着至关重要的作用。中央记忆型T细胞(central memory T cell,Tcm)是幼稚T细胞经过抗原激活后,产生的具有长期记忆性的、并能够归巢到淋巴结接受抗原再刺...记忆T细胞(memory T cell,Tm)作为人体免疫系统中的一个组成部分,在免疫应答中发挥着至关重要的作用。中央记忆型T细胞(central memory T cell,Tcm)是幼稚T细胞经过抗原激活后,产生的具有长期记忆性的、并能够归巢到淋巴结接受抗原再刺激的T细胞。肿瘤免疫治疗的抗肿瘤作用及不良反应的发生与T细胞功能密切相关,Tcm不仅是介导免疫应答的防线,其作为疗效预测生物标记物的研究也取得了相当大的进展。目前肠道菌群对肿瘤免疫治疗的影响备受关注,肠道菌群及其代谢产物通过影响肿瘤微环境调控疗效,其在免疫细胞层面的机制值得探究。本文对Tcm在组织中的分化、表面标记,在肿瘤免疫治疗中的作用及其与肠道菌群的联系等方面的研究进展进行综述。展开更多
目的研究肝癌患者外周血中CD45RO^+记忆T细胞(memory T cells,Tm)表面标志CD45RO、CD62L和CCR7的表达,以了解CD45RO^+CD62L~^+CCR7^+T细胞(中央型记忆T细胞,central memory T cells,TCM)和CD45RO^+CD62L^-CCR7^-T细胞(效应型记忆T细胞,e...目的研究肝癌患者外周血中CD45RO^+记忆T细胞(memory T cells,Tm)表面标志CD45RO、CD62L和CCR7的表达,以了解CD45RO^+CD62L~^+CCR7^+T细胞(中央型记忆T细胞,central memory T cells,TCM)和CD45RO^+CD62L^-CCR7^-T细胞(效应型记忆T细胞,effector memory T cells,TEM)亚群在肝癌患者外周血中的分布特点。方法获取正常人健康志愿者(正常对照组)28例和2011年8月至2013年8月的初诊慢性乙型病毒性肝炎患者(乙肝对照组)28例以及同期患有乙肝的肝癌患者(乙肝肝癌组)30例的外周静脉血,分离外周血单个核细胞(PBMC)。用多色流式细胞仪检测技术(polychromatic flow cytometry,PFC)检测外周血PBMC中记忆T淋巴细胞表面标志CD3、CD4、CD8、CD45RO、CD62L、CCR7的表达情况。结果乙肝肝癌组外周血PBMC中,CD4^+T淋巴细胞和CD8^+T淋巴细胞分别占外周血PBMC的比例显著高于乙肝对照组(28.15±12.32 VS 11.56±5.78,29.33±15.54 VS 13.11±6.64)(P<0.001,P=0.019);而较正常对照组无明显差异。乙肝肝癌组外周血PBMC的T淋巴细胞中CD4^+T_(EM)占CD4^+T记忆淋巴细胞比例显著高于乙肝对照组、正常对照组(93.78±5.63 VS 75.82±19.74,93.78±5.63 VS 68.25±15.65)(P=0.001,P=0.018),而CD4+TCM则显著低于乙肝对照组、正常对照组(0.55±1.02 VS 4.87±6.28,0.55±1.02VS 4.16±3.49)(P均小于<0.001)。三组的CD4^+TEM记忆细胞占外周血PBMC中CD4^+T记忆淋巴细胞的比例显著高于CD4^+T_(CM)记忆细胞占外周血PBMC中CD4^+T记忆淋巴细胞的比例(91.78±5.63 VS 0.55±1.02,75.82±19.74 VS 4.87±6.28,68.25±15.65 VS 4.16±3.49)(P值均小于0.001)。乙肝肝癌组外周血PBMC的T淋巴细胞中CD8^+TEM和CD8^+TCM占CD8^+T记忆淋巴细胞比例与乙肝对照组、正常对照组相比,差异均无显著意义。三组的CD8+TEM记忆细胞占外周血PBMC中CD8^+T记忆淋巴细胞的比例显著高于CD8^+TCM记忆细胞占外周血PBMC中CD8^+T记忆淋巴细胞的比例(80.12±13.56 VS 3.25±2.47,79.21±11.34 VS 4.44±7.19,73.33±16.88 VS 2.66±3.10)(P值均小于0.001)。结论在乙肝肝癌组、乙肝对照组和正常对照组中,无论是CD4^+T记忆淋巴细胞,还是CD8^+T记忆淋巴细胞,均以TEM占绝大多数,而TCM比例很小。乙肝肝癌组中,CD4^+TEM显著高于乙肝对照组和正常对照组,CD4^+TCM显著低于乙肝对照组和正常对照组,而CD8^+TEM和CD8^+TCM则与乙肝对照组、正常对照组均无明显差异。展开更多
基金National Natural Science Foundation of China(81871784 and 82171822)CAMS Major Collaborative Innovation Project(2016-I2M-1-011,China)+2 种基金Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study Project(BZ0150,China)Graduate Innovation Fund(20181007-05,China)Yunnan Science and Technology Talent and Platform Program(202105AG070012,China)。
文摘Berberine(BBR)as one of the most effective natural products has been increasingly used to treat various chronic diseases due to its immunosuppressive/tolerogenic activities.However,it is unknown if BBR can be applied without abrogating the efforts of vaccination.Here we show that priming of CD8^(+)T cells in the presence of BBR lead to improved central memory formation(Tcm)with substantially reduced effector proliferation,primarily orchestrated through activation of AMPK and Stat5.Tcm derived from vaccinated mice fed with BBR were able to adoptively transfer protective immunity to naIve recipients.Vaccination of BBR-fed mice conferred better memory protection against infection without losing immediate effector efficacy,suggesting appreciable benefits from using BBR in vaccination.Thus,our study may help to lay the groundwork for mechanistic understanding of the immunomodulatory effects of natural products and their potential use as adjuvant that allows the design of novel vaccines with more desirable properties.
文摘记忆T细胞(memory T cell,Tm)作为人体免疫系统中的一个组成部分,在免疫应答中发挥着至关重要的作用。中央记忆型T细胞(central memory T cell,Tcm)是幼稚T细胞经过抗原激活后,产生的具有长期记忆性的、并能够归巢到淋巴结接受抗原再刺激的T细胞。肿瘤免疫治疗的抗肿瘤作用及不良反应的发生与T细胞功能密切相关,Tcm不仅是介导免疫应答的防线,其作为疗效预测生物标记物的研究也取得了相当大的进展。目前肠道菌群对肿瘤免疫治疗的影响备受关注,肠道菌群及其代谢产物通过影响肿瘤微环境调控疗效,其在免疫细胞层面的机制值得探究。本文对Tcm在组织中的分化、表面标记,在肿瘤免疫治疗中的作用及其与肠道菌群的联系等方面的研究进展进行综述。
文摘目的研究肝癌患者外周血中CD45RO^+记忆T细胞(memory T cells,Tm)表面标志CD45RO、CD62L和CCR7的表达,以了解CD45RO^+CD62L~^+CCR7^+T细胞(中央型记忆T细胞,central memory T cells,TCM)和CD45RO^+CD62L^-CCR7^-T细胞(效应型记忆T细胞,effector memory T cells,TEM)亚群在肝癌患者外周血中的分布特点。方法获取正常人健康志愿者(正常对照组)28例和2011年8月至2013年8月的初诊慢性乙型病毒性肝炎患者(乙肝对照组)28例以及同期患有乙肝的肝癌患者(乙肝肝癌组)30例的外周静脉血,分离外周血单个核细胞(PBMC)。用多色流式细胞仪检测技术(polychromatic flow cytometry,PFC)检测外周血PBMC中记忆T淋巴细胞表面标志CD3、CD4、CD8、CD45RO、CD62L、CCR7的表达情况。结果乙肝肝癌组外周血PBMC中,CD4^+T淋巴细胞和CD8^+T淋巴细胞分别占外周血PBMC的比例显著高于乙肝对照组(28.15±12.32 VS 11.56±5.78,29.33±15.54 VS 13.11±6.64)(P<0.001,P=0.019);而较正常对照组无明显差异。乙肝肝癌组外周血PBMC的T淋巴细胞中CD4^+T_(EM)占CD4^+T记忆淋巴细胞比例显著高于乙肝对照组、正常对照组(93.78±5.63 VS 75.82±19.74,93.78±5.63 VS 68.25±15.65)(P=0.001,P=0.018),而CD4+TCM则显著低于乙肝对照组、正常对照组(0.55±1.02 VS 4.87±6.28,0.55±1.02VS 4.16±3.49)(P均小于<0.001)。三组的CD4^+TEM记忆细胞占外周血PBMC中CD4^+T记忆淋巴细胞的比例显著高于CD4^+T_(CM)记忆细胞占外周血PBMC中CD4^+T记忆淋巴细胞的比例(91.78±5.63 VS 0.55±1.02,75.82±19.74 VS 4.87±6.28,68.25±15.65 VS 4.16±3.49)(P值均小于0.001)。乙肝肝癌组外周血PBMC的T淋巴细胞中CD8^+TEM和CD8^+TCM占CD8^+T记忆淋巴细胞比例与乙肝对照组、正常对照组相比,差异均无显著意义。三组的CD8+TEM记忆细胞占外周血PBMC中CD8^+T记忆淋巴细胞的比例显著高于CD8^+TCM记忆细胞占外周血PBMC中CD8^+T记忆淋巴细胞的比例(80.12±13.56 VS 3.25±2.47,79.21±11.34 VS 4.44±7.19,73.33±16.88 VS 2.66±3.10)(P值均小于0.001)。结论在乙肝肝癌组、乙肝对照组和正常对照组中,无论是CD4^+T记忆淋巴细胞,还是CD8^+T记忆淋巴细胞,均以TEM占绝大多数,而TCM比例很小。乙肝肝癌组中,CD4^+TEM显著高于乙肝对照组和正常对照组,CD4^+TCM显著低于乙肝对照组和正常对照组,而CD8^+TEM和CD8^+TCM则与乙肝对照组、正常对照组均无明显差异。
