J Gastroenterology: CCL19可以增强CD8+T细胞反应并加速 HBV 清除

2021-07-15 MedSci原创 MedSci原创

全世界约有 2.5 亿人感染乙型肝炎病毒 (HBV),并且处于肝变性的各个阶段,比如肝脂肪变性、肝硬化、终末期肝功能衰竭或肝细胞癌等。

      全世界约有 2.5 亿人感染乙型肝炎病毒 (HBV),并且处于肝变性的各个阶段,比如肝脂肪变性、肝硬化、终末期肝功能衰竭或肝细胞癌等。目前得到世卫组织批准的治疗策略包括干扰素-α(IFN-α),核苷和核苷酸类似物提供的功效有限。在原发性 HBV 感染中,病毒在大约 90% 的成年人中被完全根除,其余个体会出现病毒持续存在和疾病进展。HBV 反应性 CD8+T 细胞反应在感染开始时在病毒清除中起关键作用,而这些反应在慢性感染期间变得相当弱,这称为 CD8+T 细胞耗竭。趋化因子配体 19 (CCL19) 是一种白细胞趋化剂,在细胞运输和白细胞活化中起关键作用。功能失调的 CD8+T 细胞在持续性 HBV 感染中起关键作用。然而,CCL19 激活的免疫是否可以清除 HBV 尚不清楚。

 

      本项研究评估了 CCL19 对 HBV 感染患者 PBMC 激活的影响,还研究了 CCL19 如何影响慢性乙型肝炎 (CHB) 小鼠模型中的 HBV 清除和调节 HBV 反应性 T 细胞。此外,C-C 趋化因子受体 7 (CCR7) 敲低小鼠被用来阐明 CCL19/CCR7 轴诱导免疫激活的潜在机制。

 

      从体外实验中,研究人员发现 CCL19 将来自患者的反应性 IFN-γ+CD8+T 细胞的数量提高了大约两倍,而 CCR7 敲低 (LV-shCCR7) 和 LY294002 部分抑制了 IFN-γ 分泌。在小鼠中,CCL19 过表达导致肝内 HBV 的快速清除,这可能是通过增加肝内 CD8+T 细胞比例、降低血液中 PD-1+CD8+T 细胞的频率和削弱对肝 APC 的抑制导致的。在 CCL19 过表达和 CCR7 敲低 (AAV-shCCR7) CHB 小鼠中,CD8+T 细胞活化诱导的细胞死亡 (AICD) 增加,并观察到高水平的 Ag 反应性 TNF-α 和低水平的 CD8 +调节性 T (T reg ) 细胞的增加。

 

      本研究的结果提供了对 CCL19/CCR7 轴如何调节宿主免疫系统的新的见解,HBV患者可能通过克服 T 细胞耐受性来促进 HBV 的治疗。

 

 

原始出处:

Yan Yan. Et al. CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance. Journal of Gastroenterology.2021.

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    2021-09-19 gds2009
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  4. 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channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8524, encryptionId=f9d08524be, topicName=HBV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Sun Mar 20 09:39:34 CST 2022, time=2022-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1051116, encodeId=332310511163f, content=<a href='/topic/show?id=fe74436549' target=_blank style='color:#2F92EE;'>#CD8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4365, encryptionId=fe74436549, topicName=CD8+T)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Tue Sep 14 14:17:06 CST 2021, time=2021-09-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1649529, encodeId=615016495298c, content=<a href='/topic/show?id=5b05180159a' target=_blank style='color:#2F92EE;'>#T细胞反应#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18015, encryptionId=5b05180159a, topicName=T细胞反应)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cce623855314, createdName=millore, createdTime=Sat Oct 02 22:39:34 CST 2021, time=2021-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1505288, encodeId=fc061505288c3, content=<a href='/topic/show?id=7730e85412' target=_blank style='color:#2F92EE;'>#Gastroenterology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=7854, encryptionId=7730e85412, topicName=Gastroenterology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sat Jul 17 01:39:34 CST 2021, time=2021-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605415, encodeId=4345160541595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Jul 17 01:39:34 CST 2021, time=2021-07-17, status=1, ipAttribution=)]
    2022-02-27 许安
  5. 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  6. 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channel=null, level=null, likeNumber=60, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8524, encryptionId=f9d08524be, topicName=HBV)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e87531, createdName=klivis, createdTime=Sun Mar 20 09:39:34 CST 2022, time=2022-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1051116, encodeId=332310511163f, content=<a href='/topic/show?id=fe74436549' target=_blank style='color:#2F92EE;'>#CD8+T#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=56, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4365, encryptionId=fe74436549, topicName=CD8+T)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20211210/ede9c51184aa4f54ae6c1164cfb8eeac/967dbf3eff2943c7bf3ccfec3a776ab0.JPG, createdBy=a33789389, createdName=病毒猎手, createdTime=Tue Sep 14 14:17:06 CST 2021, time=2021-09-14, status=1, ipAttribution=), 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createdAvatar=null, createdBy=5fc29706655, createdName=chaojitidian, createdTime=Sat Jul 17 01:39:34 CST 2021, time=2021-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605415, encodeId=4345160541595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Sat Jul 17 01:39:34 CST 2021, time=2021-07-17, status=1, ipAttribution=)]
    2022-03-20 klivis
  7. 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NEJM:Novavax重组蛋白疫苗保护力89.7%,对变种新冠病毒有效!

疫苗对B.1.1.7变体的有效率为86.3%,对非B.1.1.7菌株的有效率为96.4%。

疫苗对癌症患者安全有效,花粉在病毒传播中的作用不可忽视:新冠研究一周进展

近日,发表于《癌细胞》(Cancer Cell)的一项针对200名已确诊癌症患者的研究阐明了新冠疫苗对癌症患者的安全性及有效性。

BMC Infect Dis:母体脊灰病毒抗体对婴儿对脊灰病毒疫苗免疫反应的影响

母体小儿麻痹病毒抗体可以为新生儿提供被动免疫,使其在出生后的头几个月免受小儿麻痹病毒感染,但它们也可能损害婴儿对小儿麻痹病毒疫苗的免疫反应。本研究中,研究人员汇总了基于Sabin毒株的脊髓灰质炎灭活疫