Science Translational Medicine:外来的免疫细胞好感染?组织驻留记忆T细胞免疫监视大脑实质

2022-04-21 周科 “神经周K”公众号

2022年4月13日Science Translational Medicine杂志背靠背同期发表两篇文章,揭示了T-RM细胞依赖于CD4 + 辅助T 细胞参与中枢神经免疫系统疾病的病理过程。

组织驻留记忆T细胞(T-RM细胞)是一类驻留于组织的、新的长效记忆T细胞,细胞表面富集表达CD69 和 CD103。与效应记忆T 细胞存在不同转录组学特 。在进入组织之前,T- RM细胞经历转录程序化的分化过程,促进其长期驻留。在抗原刺激下T-RM 细胞迅速激活,进行细胞增殖,处于局部警戒状态,引起免疫细胞的募集,最终产生组织特异性抗感染反应。

除存在外周组织中,大脑、血脑屏障也存在T- RM细胞。在哮喘、牛皮癣、白癜风、炎症性肠病和1型糖尿病等慢性炎症或自身免疫性疾病中均存在T- RM细胞。

2022年4月13日Science Translational Medicine杂志背靠背同期发表两篇文章,揭示了T-RM细胞依赖于CD4 + 辅助T 细胞参与中枢神经免疫系统疾病的病理过程。

法国图卢兹大学Roland S. Liblau研究团队在自身免疫性脑炎患者大脑出现大量的T- RM细胞浸润,进一步通过神经自身免疫动物模型模拟自身反应性组织驻留 CD8 + T 细胞持续出现在局灶性神经炎症部位,并引起神经元进行性丢失。

他们发现自身免疫性脑炎患者大脑存在显着的T细胞浸润,其中约60%为CD8阳性的T-RM细胞,并靠近神经元。Orex-HA小鼠是一种下丘脑食欲素能神经元选择性地表达自身抗原血凝素 (HA),在静脉注射 HA 特异性效应 CD8 阳性 T 细胞后,下丘脑区域CD8 阳性 T 细胞数量迅速增加,随后注射后第8天明显表达CD69 和 CD103,这就表明CD8阳性的T- RM细胞驻留在下丘脑中。有意思的是,注射后第8天下丘脑食欲素能神经元出现明显的神经元丢失。

通过清除接受T细胞刺激后Orex-HA小鼠外周血液中CD8 阳性 T 细胞后并不能减少下丘脑神经元的丢失。CD4 + 辅助T 细胞在T- RM细胞发育和维持期发挥重要作用。尽管早期同时清除外周CD8 阳性 T 细胞和CD4 + 辅助T 细胞并不能阻止下丘脑中HA 特异性效应 CD8 阳性 T 细胞的分化,但是在清除1个月后下丘脑T- RM细胞数量明显减少,食欲素能神经元丢失也减少,这就表明下丘脑驻留的T- RM细胞依赖CD4 + 辅助T 细胞引起神经元丢失。

淋巴细胞性脉络丛脑膜炎是由淋巴细胞性脉络丛脑膜炎病毒(LCMV)引起的急性传染病。同期,瑞士日内瓦大学Doron Merkler研究团队利用LCMV靶向大脑星形胶质细胞上自身抗原诱发免疫反应,促进静息态T-RM细胞数量的增加,引起运动功能障碍。

他们发现在多发性硬化症患者急性活跃期和视神经脊髓炎谱系障碍患者中均存在大量的T-RM细胞。

在清除外周CD8阳性T细胞并不会影响T-RM细胞的扩增,也不会改变小鼠的运动障碍。然而,在清除CD4 + 辅助T细胞后,T-RM细胞数量逐渐减少,并不能增殖分化呈最终的效应状态。

总的来说,上述两篇文章利用不同的免疫效应动物模型诱发大脑T-RM细胞的驻留,出现局部神经免疫反应模拟出神经免疫疾病状态,发现CD4 + 辅助T细胞是T-RM细胞的驻留在中枢神经系统重要辅助因子。

原始出处:

1. Frieser et al.Tissue-resident CD8 + T cells drive compartmentalized and chronic autoimmune damage against CNS neurons. Sci. Transl. Med. 14, eabl6157 (2022).

2. Vincenti et al. Tissue-resident memory CD8 + T cells cooperate with CD4 + T cells to drive compartmentalized immunopathology in the CNS. Sci. Transl. Med. 14, eabl6058 (2022).

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time=2022-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376438, encodeId=210213e643892, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407643, encodeId=1665140e6437d, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577887, encodeId=87d915e78876f, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=)]
    2022-07-02 kalseyzl
  4. 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  5. 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time=2022-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376438, encodeId=210213e643892, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407643, encodeId=1665140e6437d, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577887, encodeId=87d915e78876f, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=)]
    2022-12-06 jeanqiuqiu
  6. 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time=2022-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376438, encodeId=210213e643892, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407643, encodeId=1665140e6437d, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577887, encodeId=87d915e78876f, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=)]
    2023-02-09 bsmagic9140
  7. 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  8. [GetPortalCommentsPageByObjectIdResponse(id=1796076, encodeId=ab121e960765e, content=<a href='/topic/show?id=8c201e758e5' target=_blank style='color:#2F92EE;'>#translational#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17758, encryptionId=8c201e758e5, topicName=translational)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d81c2500028, createdName=12498561m32(暂无昵称), createdTime=Thu Jul 28 02:06:01 CST 2022, time=2022-07-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795954, encodeId=f25c1e9595476, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, 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href='/topic/show?id=3ca31e71903' target=_blank style='color:#2F92EE;'>#TRA#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17719, encryptionId=3ca31e71903, topicName=TRA)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=757b24868428, createdName=bsmagic9140, createdTime=Thu Feb 09 15:06:01 CST 2023, time=2023-02-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1744952, encodeId=73701e44952a0, content=<a href='/topic/show?id=ec5e848002b' target=_blank style='color:#2F92EE;'>#脑实质#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=84800, encryptionId=ec5e848002b, topicName=脑实质)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=0ada35479922, createdName=muzishouyi, createdTime=Fri Nov 25 21:06:01 CST 2022, time=2022-11-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376438, encodeId=210213e643892, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1407643, encodeId=1665140e6437d, content=<a href='/topic/show?id=f150e779256' target=_blank style='color:#2F92EE;'>#细胞免疫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77792, encryptionId=f150e779256, topicName=细胞免疫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=b9362684728, createdName=tulenzi, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577887, encodeId=87d915e78876f, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Sat Apr 23 06:06:01 CST 2022, time=2022-04-23, status=1, ipAttribution=)]
    2022-04-23 jichang
  9. 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  10. 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