T細胞亞群進展及臨床意義課件

1、T細胞亞群進展及臨床意義1映碼刻績有壯翰抒牧噎宮妄絕夾剮封淄恩閥巨甄濟泛駭帕起整溺攣了俄衙T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第1頁，共41頁。醫(yī)學(xué)免疫學(xué)上海第二醫(yī)科大學(xué)免疫教研室2薊擱辨氖撞肺心熄史拄樟危著裸腎墨贈蟬蠶彪循義危乍嗣婿邀聾牟羨喉效T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第2頁，共41頁。醫(yī)學(xué)免疫學(xué)上海第二醫(yī)科大學(xué)免疫教研室3拴球錦隘凡表盲蝴縷骯促葫末礦倘模檢貶摟碗據(jù)剔在夢灶扼顯知熊椒漠靈T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第3頁，共41頁。剩綿白吶實蘊于賓弱矚狠歸養(yǎng)翌托淮幅罪挫呂艱缸上復(fù)鞘邵吩模襄穴提十T細胞亞群進展及臨床意義T細胞亞群進展及臨床

2、意義第4頁，共41頁。T 細胞亞群與功能 根據(jù)TCR種類 TCR-1（TCR），TCR-2（TCR ）根據(jù)TCR-2（TCR ）表達CD4或CD8的不同 CD4+T分子表型為CD2、CD3、CD4 CD8+T分子表型為CD2、CD3、CD8 根據(jù)功能 Th、Tc、Ts、TDTH 根據(jù)對抗原的應(yīng)答不同 初始T細胞、抗原活化過的T細胞、記憶性T細胞這葫犬響累切壘道踢夠虞鞭聾撐制熔川聲夠鞘暑剛幀券切莖履杭授霓才眩T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第5頁，共41頁。T細胞亞群CD4 + 、CD8 +亞群 CD4+T細胞識別由1317個氨基酸殘基組成的抗原肽，并受自身的MHC II類限制。

3、CD8 + T細胞識別810個氨基酸組成的抗原肽，并受MHC I類限制。TCRT細胞和TCRT細胞 6做覽妝瓷酬喪撂松絕咸敝朵新痕硒抗妝掐嗆肚巋粥偷頁乍滑橋灼朽泡暈十T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第6頁，共41頁。Th、Tc、Ts和TDTH細胞Th細胞 根據(jù)所分泌的細胞因子不同，將其分為Th0、Th1和Th2亞型。Tc細胞 Tc1細胞主要分泌IFN；Tc2細胞則主要分泌IL-4、IL-5和IL-10。Ts細胞 TDTH 主要為CD4 + Th17棵補俞雪聞博俏字魔算曬壽礬拂脫閩活荒敦擠勾敬薦鋅跳雕銷沫趟茬明焦T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第7頁，共41頁。（

4、一）TCR T細胞 和 TCR T細胞TCR 極大多態(tài)性 極少多態(tài)性分布 外周血 60-70% 5-15% 組織 外周淋巴組織 黏膜上皮表型 CD3+CD2+ 100% 100% CD4+CD8- 60-65% 20-50% CD4-CD8+ 30-35% 20-50% CD4-CD8- 5% 50%識別抗原 8-17aa 簡單多肽、HSP、脂類、多糖MHC限制 經(jīng)典MHC分子 MHC類似分子輔助細胞 Th細胞殺傷細胞 Tc細胞 Tc細胞特性 TCR T細胞TCRT細胞轅虛焚瘤翁率蘊換津疙拒純集蒜惱途藥及償?shù)冻烂Ц范肜芴矣罕螛菞椏碩細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第8頁，共41

5、頁。按CD分子不同按功能不同T細胞CD4T細胞CD8T細胞輔助性T細胞(Th)細胞毒性T細胞(CTL或Tc)抑制性T細胞(Ts)貪瓊東坊瞳疆砰腋丈沛氮瓤袱躥簽風陽染們腸拳載哥禿紗次皋槽乒全子溯T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第9頁，共41頁。 CD4T細胞 CD表型：CD3+CD4+CD8-，主要為Th細胞亞群 識別抗原時受MHC-類分子限制 通過分泌細胞因子發(fā)揮效應(yīng)功能 CD4T細胞(部分)也具有細胞殺傷功能作用特點1.CD4+Th細胞及其功能兆晦隊窩酵耽發(fā)刺撿酌肘懦瑤味宵菠涼售摟椽臨墊磨劣彈協(xié)墻史暴尋我堂T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第10頁，共41頁。

6、2. CD8T細胞 CD表型：CD3+CD8+CD4-，主要為CTL細胞亞群 識別抗原時受MHC- 類分子限制 免疫調(diào)節(jié)作用, 如釋放IFN-、TNF-和TNF-等細胞因子 具有細胞殺傷功能作用特點廓氣鞠錐汪彰旗歲貧齒輻鐮巧敲郭謹娛餃孟份墩褲窘朔昆扔璃肺適進攢阻T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第11頁，共41頁。CD8+殺傷性T細胞 CTL的主要作用是直接殺傷靶細胞，有兩種機制：細胞裂解和細胞凋亡12脾瞄賂雞菜泌沛位土粘疥渺丘韋陡脫譜德婿偉馱命親睜甩氛穗麻尼奮煤皂T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第12頁，共41頁。CTL 殺傷靶細胞的機制13廳丙瞧嘛頃碼家浮則驚

7、膊殃疵循汰送舌嘿琵己鍬囑潔慢虜挖造斡島訊評此T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第13頁，共41頁。CD8+Tc細胞（CTL）及其功能免疫應(yīng)答的主要效應(yīng)細胞，在腫瘤免疫和抗病毒免疫中發(fā)揮重要作用（抗腫瘤）作用特點：特異直接殺傷靶細胞，在殺傷過程中自身不受損傷，可反復(fù)連續(xù)殺傷。 作用機制：細胞裂解（cytolysis） 細胞凋亡 （apoptosis）楚盾慧瞞譬擬各遼擇視困騎鑿潞膽談寡欣棚田添岔滬降星解首保輛討洞賢T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第14頁，共41頁?？鼓[瘤亢籮傳鴛訛胸版豈糠鈴微沁瑪緣串誦必立溶淬墓棚嗡搬務(wù)輻違堂歲咐糕鍘T細胞亞群進展及臨床意義T細胞亞群

8、進展及臨床意義第15頁，共41頁。Introduction of Th1/Th2 cellsIn 1986, T.R. Mosman and R.L. Coffman observed that individual clones of mouse helper T cells could be separated into two classes depending upon the specific cytokines the cells secrete in response to antigenic stimulation.毒迫加虹墊瓜駱寓味潞晝吸舀堿籬攆加聳淤康壬孝卸愈頁泣灌鼻譜諾干

9、鉸T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第16頁，共41頁。Induction of Th1 and Th2 ResponsesTh2Th1AntigensIL-4IL-12IFN-APCNave CD4Effector CellsSignal 2Signal 1IL-2IFN-IL-4IL-5IL-10Cellular Immune ResponsesHumoral Immune Responses谷而餐蛋迅視真遁訪值敢戚煤詠舶裝此掀闡優(yōu)財諜把罵劉癟蘆碘巖嶺窮脆T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第17頁，共41頁。Leishmania major Infection

10、in Mice Provides a Useful Model to Study Th1 and Th2 Differentiation and Memory in vivo合料甄嵌輪淀控牲笑盈誕烴緝樸莫懈凰脫滁亦柬曠擲脊猶仔怔偏仙否伐堂T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第18頁，共41頁。Leishmania major infection: Mouse ModelsBalb/CBL/6Th 1 responseDeathRecoveryTh 2 responseIL-12IL-12/IFN-熙涅椰語煩丫戊秉霞圣春祭咱娃息煤礎(chǔ)鄲忻籬鉗界捶燼康出哭合遣倍糠北T細胞亞群進展及臨床意

11、義T細胞亞群進展及臨床意義第19頁，共41頁。Signaling of IL-12 Receptor12TYK2JAK2p40p35STAT4PPYStat4Stat4PPYYIFN-ProductionExpression1: Expressed on Th1, Th2, N.K., and B cells2: Expressed on activated Nave T, Th1, and N.K. cellsRegulationEnhanced by: activation of -CD28, IL-2, IL-7, IL-15, IFN- (mouse), IFN- (human)Inh

12、ibited by: IL-4, IL-10, TGF-, PGE2, Dex討歌數(shù)度郁滿照高烘褐罩鈾無論急坷窗閉柏角策斃方皮茁州姿鞏髓啊撓斥T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第20頁，共41頁。Cytokines On Th1 Cell DevelopmentPathogenAPC CD4+T CellSTAT4TCRIFN-IFN-+IL-27TCCR/WSX-1IL-12IL-12IL-23IL-12IL-18IL-18Nave CD4+Th1Th1 EffectorIL-12R12IL-18RIL-18RIL-12R1IL-12R1IL-12R122STAT1T-betI

13、FN-T-betSTAT4STAT4NFKBGADD45p3BIRAKNFKB如果敲除IL-12基因細胞免疫功能下降80%沫驗呸舍鯉暮琶核成生稿拒賊夜薔友評哎碼目禿鞏貯薔謎冤贏麻系演夏穿T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第21頁，共41頁。 T淋巴細胞的功能(1)介導(dǎo)細胞免疫應(yīng)答(2)分泌細胞因子參與免疫調(diào)節(jié)22鍘痰徑準鑰跟玫豎輝危漓熱葉悍鎮(zhèn)帕懂符號展期噸找徽契痙權(quán)誰炕井驟莖T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第22頁，共41頁。Interleukin-9 (IL-9)-producing T cells (Th9 Cells) 肥大細胞、過敏反應(yīng)向下般縮刃碼嗓美浙衰

14、募桐力訖辦檢宮夕枉硼桿瑟弱牧希飯部判滇喳碘與T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第23頁，共41頁。IntroductionRecently, two reports described a discrete subset of interleukin-9(IL-9)-producing T cells that might be closely related to the TH2-cell lineage.These IL-9-producing T cells seem to be a distinct population that does not show the ch

15、aracteristics of other described T-cell subsets-“TH9” cells.高叛菏牽訛薛受糜頻服去跳腔馭白萄騎御峻陳漣撤猛嚴該麗捏釩遮正撓白T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第24頁，共41頁。25稻妙馱分叼撲瘴聯(lián)寥臆縫搬叔足搏仰笛幢祝無鳳線兼桿額農(nóng)伺靠檢丁派模T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第25頁，共41頁。26稗忌亢辭食亮繃訣撓品歧硅措也溢磋界蔬陵出汰鐐榨畸糧謾夜賂澇鉀厲砌T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第26頁，共41頁。TGF- deviates TH2 cells to a “TH-9” fa

16、teIL-9-producing T cells could be generated from TH2 cells that were exposed to TGF- in vitro, even when the TH2 cells were highly polarized.IL-4 inhibits TGF-induced Foxp3+ T cellsIL-4 actively inhibits the induction of Foxp3 in the presence of TGF-.The inhibition of Foxp3 expression by IL-4 is med

17、iated through the IL-4-STAT6 pathway.The Foxp3 can directly interact with GATA-3 and this association inhibits GATA-3 mediated transactivation of IL-5, which is one of its target genes.翅盎蒜緬邏派肩效孽烏邯纓磺貴孟藐茄扛薄誨伍懦亭者頭逞兒漱囂墜鄰裹T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第27頁，共41頁。TTcTh0Tc2Tc1TregTh2Th1TregCD4+CD8+CD4+25+28效應(yīng)-調(diào)控

18、過強和過弱剁鴦咀畢齲椅沏焦倫蹈例容移陋阿劃淖褒番化綱援潮倆儒向隆撇蕩貯帶淪T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第28頁，共41頁。The Role of Suppressor or Regulatory T Cells (Treg) in Immunity豌貯肆擦積膘懲培置沒蓋恃梆引犢被唇顆柑攔仕俏驟侈屎拌斂靠筆誅茅符T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第29頁，共41頁。IntroductionRegulation of immune responses to self-antigen is a complex processMaintaining self-tole

19、ranceRetaining the capacity to mount immune responses against invading microorganisms驟歲嘲攣侄辱馴聘痛錦己樣鴛借鬧獻卉糯塵葡杏寫欺尿魚郴位樞棗堯秀酌T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第30頁，共41頁。Discovery of Suppressor T CellsIn 1995, Sakaguchi et al made the seminal observation: The transfer of CD4+ T cells which had been depleted of the the

20、 minor subpopulation (10%) of cells to nu/nu recepients induced organ-specific autoimmune diseases in the majority of recipients.The minor subpopulation of cells are CD4+CD25+ T cells.樓貿(mào)陜飛娠抽螺拷莆嶼孿玄醉煥略濕魄窩到贛胚滲敷負菊亮馴扎刮鴿拆蜘T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第31頁，共41頁。Discovery of Suppressor T cells洱撫玉豆毫豁音歇剩囑純荒秒晦橙籮嗽未虱

21、拘坎澄熒忱爽丹纓纂田仟菩娥T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第32頁，共41頁。CD4+CD25+ Regulatory T cellsA unique lineage of regulatory T cells capable of maintaining self tolerance in vivo33邑淳促裂商嚙閨媚鐵蛀皇雄氣妙蘋蒸胺冉祖輔僳咳僻泅境口糯粕舷筒弛置T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第33頁，共41頁。TCD8CD4CD4+25+Th1Tc2Tc1Th2Th3Tr1Peripheral T lymphocyte5-10%30%Th4?60%Thy

22、mus34能英繁盔汪恨才蠶階旅永屆時南保專盛喻分癱刑虞睜科攔蜒地貌嘩艦術(shù)糟T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第34頁，共41頁。Overview of phenotypes and functions of CD4+ T cellsNaveCD4Th1TrTh2IFN-Cell mediated immune responsesIL-4 IL-5 IL-10 IL-13humoral immune responseTr 1Th 3CD4+CD25+High IL-10 , low TGF-TGF-cell-cell contactNatural Tr in thymus cont

23、act-dependentAdaptive Tr in peripheral lymphoid tissue cytokines-dependant Regulatory T cells圓駐茂奸壹粕裸議汐查吠炸陪嫂廣嚙瓢頑樟院咋署寶妥鋼剛協(xié)納輥拈畝暖T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第35頁，共41頁。 CD4+CD25+ Tr cells: Comprise 5-10% of peripheral CD4 T cells in human and miceProduced in thymus as an unique lineage of CD4 T cellsSecret I

24、L-10 and/or TGF-b, but little IL-2Anergic and suppressive CD45RBlow, CTLA-4 high36限一脂閹縫循些餐爪疫名成示茫循毋判材匪泉烷勁慌券眩纖掘薯剖賒伸圈T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第36頁，共41頁。淋巴細胞及其亞群分析 T淋巴細胞及亞群： 外周血中成熟淋巴細胞主要屬于TCRT細胞，可分為Th、Ts、Treg，TCRT細胞和NK1.1T細胞等，他們都有一個共同的標志CD3。37爆冉班灰靈珍顴島肆縫驕睫壓墟懸瞞都直峽當禿柏爭趕悸只軟替晰媽藝掏T細胞亞群進展及臨床意義T細胞亞群進展及臨床意義第37頁，共41頁。a、輔助/誘導(dǎo)性T淋巴細胞（Th）占27-51%，是主要的功能亞群，主要表達CD3CD4CD8。b、抑制/細胞毒性T淋巴細胞（Ts）占15-44%，是主要的效應(yīng)性T細胞亞群，主要表達CD3CD4 CD8。c、Treg細胞是近年來新發(fā)現(xiàn)的一個T淋巴細胞亞群，具有重要的免疫調(diào)節(jié)功能，在自身免疫病、腫瘤和器官移植排斥反應(yīng)中具有重要作用，主要標志為CD4CD25FoxP3。38虎平鋤妹涪缽肩條笨撂安祭欠里夷疾樸擊況柯屹遲屋立拐逃搗蘆潭萬胚念T細胞亞群進展及臨床意