T细胞亚群进展及临床意义

1、1会计学T细胞亚群进展及临床意义细胞亚群进展及临床意义医学免疫学上海第二医科大学免疫教研室2T T 细胞亚群与功能细胞亚群与功能 根据根据TCR种类种类 TCR-1（TCR），），TCR-2（TCR ）根据根据TCR-2（TCR ）表达）表达CD4或或CD8的不同的不同 CD4+T分子表型为分子表型为CD2、CD3、CD4 CD8+T分子表型为分子表型为CD2、CD3、CD8 根据功能根据功能 Th、Tc、Ts、TDTH 根据对抗原的应答不同根据对抗原的应答不同 初始初始T细胞、抗原活化过的细胞、抗原活化过的T细胞、记忆性细胞、记忆性T细胞细胞56TCR 极大多态性极大多态性 极少多态性极少多

2、态性分布分布 外周血外周血 60-70% 5-15% 组织组织 外周淋巴组织外周淋巴组织 黏膜上皮黏膜上皮表型表型 CD3+CD2+ 100% 100% CD4+CD8- 60-65% 20-50% CD4-CD8+ 30-35% 20-50% CD4-CD8- 5% 50%识别抗原识别抗原 8-17aa 简单多肽、简单多肽、HSP、脂类、多糖、脂类、多糖MHC限制限制 经典经典MHC分子分子 MHC类似分子类似分子辅助细胞辅助细胞 Th细胞细胞杀伤细胞杀伤细胞 Tc细胞细胞 Tc细胞细胞TCRT细胞细胞抑制性抑制性T细胞细胞(Ts)1.CD41.CD4+ +ThTh细胞及其功能细胞及其功能1

3、1CTL 杀伤靶细胞的机制杀伤靶细胞的机制12CD8CD8+ +TcTc细胞（细胞（CTLCTL）及其功能）及其功能免疫应答的主要效应细胞免疫应答的主要效应细胞，在肿，在肿瘤免疫和抗病毒免疫中发挥重要瘤免疫和抗病毒免疫中发挥重要作用（作用（抗肿瘤抗肿瘤）作用特点：作用特点：特异直接杀伤靶细特异直接杀伤靶细胞，在杀伤过程中自身不受损胞，在杀伤过程中自身不受损伤，可反复连续杀伤。伤，可反复连续杀伤。 作用机制：作用机制：细胞裂解（细胞裂解（cytolysis） 细胞凋亡细胞凋亡 （apoptosis）抗肿瘤抗肿瘤Th2Th1AntigensIL-4IL-12IFN-APCNave CD4Effec

4、tor CellsSignal 2Signal 1IL-2IFN-IL-4IL-5IL-10Cellular Immune ResponsesHumoral Immune ResponsesLeishmania major Infection in Mice Provides a Useful Model to Study Th1 and Th2 Differentiation and Memory in vivoBalb/CBalb/CBL/6BL/6Th 1 responseDeathDeathRecoveryRecoveryTh 2 responseIL-12IL-12/IFN-12TY

5、K2JAK2p40p35STAT4PPYStat4Stat4PPYYIFN-ProductionExpression 1: Expressed on Th1, Th2, N.K., and B cells 2: Expressed on activated Nave T, Th1, and N.K. cellsRegulationEnhanced by: activation of -CD28, IL-2, IL-7, IL-15, IFN- (mouse), IFN- (human)Inhibited by: IL-4, IL-10, TGF- , PGE2, DexPathogenAPC

6、CD4+T CellSTAT4TCRIFN-IFN-+IL-27TCCR/WSX-1IL-12IL-12IL-23IL-12IL-18IL-18Nave CD4+Th1Th1 EffectorIL-12R12IL-18RIL-18RIL-12R1IL-12R1IL-12R122STAT1T-betIFN-T-betSTAT4STAT4NFKBGADD45p3BIRAKNFKB如果敲除如果敲除IL-12基因细胞免疫功能下降基因细胞免疫功能下降80%(1)介导细胞免疫应答介导细胞免疫应答(2)分泌细胞因子参与免疫调节212425IL-4 inhibits TGF-induced Foxp3+ T

7、cellsIL-4 actively inhibits the induction of Foxp3 in the presence of TGF-.The inhibition of Foxp3 expression by IL-4 is mediated 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 targ

8、et genes.TTcTh0Tc2Tc1TregTh2Th1TregCD4+CD8+CD4+25+27效应效应-调控调控 过强和过弱过强和过弱CD4+CD25+ Regulatory T cellsA unique lineage of regulatory T cells capable of maintaining self tolerance in vivo32TCD8CD4CD4+25+Th1Tc2Tc1Th2Th3Tr1Peripheral T lymphocyte5-10%30%Th4?60%Thymus33NaveCD4Th1TrTh2IFN-Cell mediated imm

9、une 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 contact-dependentAdaptive Tr in peripheral lymphoid tissue cytokines-dependant Regulatory T cells CD4+CD25+ Tr cells: Comprise 5-10% of peripheral CD4 T cells in h

10、uman and mice Produced in thymus as an unique lineage of CD4 T cells Secret IL-10 and/or TGF-, but little IL-2 Anergic and suppressive CD45RBlow, CTLA-4 high353637383940抑制性抑制性T细胞细胞(Ts)IL-4 inhibits TGF-induced Foxp3+ T cellsIL-4 actively inhibits the induction of Foxp3 in the presence of TGF-.The in

11、hibition of Foxp3 expression by IL-4 is mediated 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.TTcTh0Tc2Tc1TregTh2Th1TregCD4+CD8+CD4+25+44效应效应-调控调控 过强和过弱过强和过弱NaveCD4Th1TrTh2IFN-Cell mediated immune responsesIL-4 IL-5 IL-10 IL-13humoral immune respons