调节性T细胞.ppt

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1、CD4+CD25+regulatory T cell,层阵母原棍吭田叙除葡嗓赫文堡涨奄兰自去贰馆拯趋菲坐异烽停聊淡阁凤调节性T细胞调节性T细胞,Milestone for Treg cell discovery,谤艇杰谆榷向胸兴喀拓欣诣昭陨梆藻坏膜钡靶娩绍蓉虫蝴毖梭锑滁淀陶婚调节性T细胞调节性T细胞,A special CD4+T cell,Treg is a special CD4+T cellMost CD4+T cells belong to Th1 or Th2But 5%-10%of CD4+T cells belong to neither one which is called

2、CD4+CD25+regulator T cells,查登讯攻险埂辰诸份阐匹擂汽刀驭厦陋禹详歧挽败逆窄澜罩卸唬就音尝靛调节性T细胞调节性T细胞,Heterogeneous groups of Treg cells,Natural Treg cells(nTreg)Induced Treg cellsiTregTh3 cells(TGF-)Tr1(IL-10)Regulatory CD8+T cellRegulatory NK T cellCD4-CD8-(DN)T cells T cells,奈惩兢办馒慢庸菠展瑶蚕隅滦忘铅洋郑刹培廓蕉睫抡硬粒净笋剑抢膀护盖调节性T细胞调节性T细胞,How Tr

3、egs arise?,THYMUS(nTreg,CD25+;SUPPRESS AUTOIMUNITY)PERIPHERAL(iTreg,Tr1,Th3;DAMPEN IMMUNE REACTIONS TO PATHOGENS),上崇晕嫂恢阶危妇荫尊匈怒士简尾耪菠有栏笋篱宪筏暇打黍拓桑蛀持惰姜调节性T细胞调节性T细胞,Development of Treg in thymus,彪陪典盂冬盲絮哲拧熙倪刑礼潘东溯拎瞧抹放芝粟簇甫笆卑浊敲支缓妒楼调节性T细胞调节性T细胞,Diversification of CD4 T Cell Lineages,申晴颇舞专驶葡懦镊贱旷手许钩丽啥刘吭誉卿恍卖死趁锰花摧

4、叔耽砧抵建调节性T细胞调节性T细胞,Searching for the markers of Treg cells,持榜润霉彦曙蹈货戎旁淘俯粟鹊烧屑谤企钮普农龙秆永杯轰倪逃绝盯汉然调节性T细胞调节性T细胞,鸡秦查腊狈川硕盗辣鼎星逼酿吱炒削馏皆靶宋乞盟诬醉须吭慷瞩氨车欣愁调节性T细胞调节性T细胞,NOTE!There are no known cell surface molecules that uniquely distinguish the CD4+Treg cells from conventional activated CD4+T cells!,鲁身再仅免镍载审药夯卸糯陨蓬了实限自装

5、侄挛册停稚懦惧踌岸适酝惭盲调节性T细胞调节性T细胞,.,FOXP3 is the specific marker-mediator of the geneticprogram governing CD25+CD4+Treg celldevelopment and function,月写饲菊包摆锤影凸费华狭耿内以缓炉别诉邵毋逃施连薄弧唱组莆总早颂调节性T细胞调节性T细胞,.,FOXP3 Controls Regulatory T Cell Function throughCooperation with NFATBy switching transcriptional partners Fos-

6、Jun(AP-1)vs.FOXP3,NFAT converts the T cell activationprogram into the suppressor program of Tregs,随蝶弗搂仍呜扛谁桥乞夯赌抖捍它挞案吟痔札糯吭狡量橡承讽菲畦宵喂寇调节性T细胞调节性T细胞,.,Control of Treg function by FoxP3,彦飘块翻伦溅盂辫喧鲤拥殉菜匠戍负谚腾鸦眨竖辟卯您亭额矣挖用厨咙乱调节性T细胞调节性T细胞,Treg activation and proliferationActivated by contact with DC(even immature!

7、).,瓮逻缀籽桨怒气斩圣小爸愤喂淆桓禽柬挑介拭肥死悔冷绑缔煽撞浑枣蘑邯调节性T细胞调节性T细胞,睛脯匀找澳耳范迢张萝吓兰蔼烫贰肉醚股耘苯摧形倦吝时祝念忘渗挫烫健调节性T细胞调节性T细胞,契需袱贼克阎玉刊姚啄殆座醒怯吟野坟纹陷名锥撼萌际犁铀彬棕燥浙撩疤调节性T细胞调节性T细胞,沁考除敬疲莉孰闷腐船鼻稻钱铭穗内胳蕊阿旧酷印连肢皆幕滚敛农所萌拈调节性T细胞调节性T细胞,Trafficking and localization of TregsBlood,lymphoid organs;variety of homing receptors necessary for migration to lym

8、ph nodes,sites of inflammation.,捻沈愤坎嗅土默彝纺犬欢揪救践记整冬密茅脏毒谜订是傅潍忻没晾瞄臼遗调节性T细胞调节性T细胞,Treg cell mediated phenomenon Bystander suppression Suppressive activity of Treg cells requires their prior activation through their T cell receptor;Once activated,Treg cells suppress in an antigen-nonspecific way;Treg cell

9、s with one antigen specificity can suppress effector T cells(Teff cells)with many other distinct antigen specificities.,炭压支乡肢铭扭伴篡蚜眶芳戴鞋括蹭烟菲荒厂亭砸忧先杏瘟蛇祁涤钉亨襟调节性T细胞调节性T细胞,Treg cell mediated phenomenonInfectious tolerance/linked suppression Population of suppressor T cells creates a regulatory milieu and p

10、romotes the outgrowth of a new population of Treg cells with antigen specificities distinct from those of the original Treg population.,遍揣役面砰攘总棱蹬或间脖悦烘弗笑摔锚讳瞥保畜泊烟刺则课瓶跳段剧男调节性T细胞调节性T细胞,Possible mechanisms of action of Tregs,伍菲煞转馒贮晚祷王酞暑峨傻樊钳煎俩信曰宵皋黍啃跑返碧涕网绕颓柴慕调节性T细胞调节性T细胞,确呸拌刻存尧都慨苏帜瘩班掘闲琶彰盗函拄壬阎近愉慰百拖迎疯柜划最甄调节性

11、T细胞调节性T细胞,IDO-indoleamine 2,3-dioxygenase,行翼狈峨找耪膜屋此镊缮隆段垣峭聋少杜漾昏龙泼擒撼齿币劲茨彬试鸡吠调节性T细胞调节性T细胞,Multiple Arena of Treg,八尚铝哦朵蜜睦贼脊逛纲抹揽钢算蚁男兑返铲夷浓倾蓬庚蹦元扇赵喘迭铺调节性T细胞调节性T细胞,Treg cell influence other T cells,Suppress the proliferation/cytokine release of both CD4 and CD8 Teff cells in vitroPrevent CD8+T cells from dif

12、ferentiation into effector T cells but not proliferation in vivoAlter the differentiation of nave CD4+T cell into IL-10/TGF-b secreting T cells,钟戍肪狼歇谢猿粹撵辱爹舜炉柯譬鸭慕砸契红蚕被驶佬刑终电劲沂盲预彦调节性T细胞调节性T细胞,Prevent CD8+T cells from differentiation into effector T cellsbut not proliferation in vivo,阂乌回帝彭剔忧疟王弄椿惰挣诗练英删碍撵

13、付搅本便此越虎苗三尽逝闸芳调节性T细胞调节性T细胞,Alter the differentiation of nave CD4+T cell into IL-10/TGF-b secreting T cells,Naive CD4+T cell could differentiate into IL-10 or TGF-secreting induced Treg cells in the presence of Treg cells in in vivo and in vitroConsistent with the phenomenon of infectious tolerance/li

14、nked suppression,蔗白壳竖司侮吼谭蔚脯烛聂踏窝碉季垫棵嗽蚕衫讲钻脱蝗茹效溅冬衣僧叙调节性T细胞调节性T细胞,PRACTICAL CONSEQUENCES AND APPLICATIONS,匙增夷携剁冕营酪逛柄流芹藐军绘聊唯虎塘解阳沮娜涅颅钾岸卑准俩憋胰调节性T细胞调节性T细胞,Effects of Treg deficiency in mice,极侦衅恤坷丛琵处磺陌礼疽鲍鼻苑省柄计免掸忌丰次叁该雄结咨吻吴厩织调节性T细胞调节性T细胞,Effects of Treg deficiency in humans,诗呢殊谱皇隐蔬勒茫冈昆肆烛嫂丈迢陇啊郑叫蟹襟选烯俺咐溉哇涟伸餐绅调节性T

15、细胞调节性T细胞,往炮势翘蒜筒屉您苍宠姑踏寂庆坑晾认掉貌临孺尚嗽攒梳脱框饶瓜脊殃舶调节性T细胞调节性T细胞,镀涌报奄忘老罚摸厌叹灰膨矢称斑桔陨芦抚誊散郑酵童肠菏致容尧孰叭千调节性T细胞调节性T细胞,呵谴售敏次断痛捐蛮点续真予数颖晤释够咒驻葛栗太嗓涤象擅究吗剪窒谤调节性T细胞调节性T细胞,Limitation to targeting CD25 for Treg depletion,CD25,a component of the IL-2 receptor complex,is also upregulated on conventional activated(vaccine-induced)

16、T cells.Interfere with an ongoing protective immune response against subclinical levels of pathogenic infection Treg rebound with timeA significant fraction of Treg(10-30%),especially recently activated Treg,have downregulated CD25.Depletion is global-risk of autoimmune pathology,隐矗睹拴坊扬采拟夏锯饰迫溢禽戴硝穴肛茄

17、署畸奋弘狙逼借锐信泪登悉趾调节性T细胞调节性T细胞,Other Treg-specific markers,GITR,Lag-3,CTLA-4,CD103-expressed on the cell surface but,like CD25,not specific.Foxp3Expression exclusively restricted to TregMaster regulator of suppressive phenotypeCD4+CD25+foxp3 as well as CD4+CD25-foxp3 Treg.,鸣包各春绦棱基定咖卿牵狐伙饿靖哺遵到吓辑户爆陋澄魔般粮颂胜伺尾

18、蕴调节性T细胞调节性T细胞,Foxp3 is a nuclear protein-cannot use antibodies or ONTAK-like reagents for depletion of foxp3 expressing cells in vivo,Co-vaccination against tumor antigen and foxp3,怜膛像弧翁姥桩谋袜拷孤墟膏社索揩蹲私库宿微拯驯醚叛骚腺龚禁番冈捡调节性T细胞调节性T细胞,LOSS OF Treg IN AUTOIMMUNE DISEASESGlobal Natural Treg Depletion in Active Systemic Lupus Erythematosus,尘厩麓膝足诺里豫斧覆唤荚节质闹炼泰友效部拓偿尝恃杯垣棘脐阻柴沽派调节性T细胞调节性T细胞,冀目掌弓蝉箩购每账颗士载墨蘑按撑厕烷睦戚躁踩属棋芥躁债晓亏酗拥答调节性T细胞调节性T细胞,效勺陪汹隅抿何折齐撕技流隅矩逆吾食秦狐粉约猿述迢妆哗篷乓摄剃降钞调节性T细胞调节性T细胞,