19 2 2007 4 Chinese Bulletin of Life Sciences Vol. 19, No. 2 Apr., 2007 1004-0374(2007)02-0174-05 exosome (1, 200062 2, 200051), exosome exosome exosome exosome exosome R392A The roles of exosomes in immune tolerance ZHAO Lihua 1,2, FAN Huahua 2 * (1 Department of Biomedical Science, School of Life Sciences, East China Normal University, Shanghai 200062, China; 2 Laboratory for Blood Engineering, Shanghai (Red cross) Blood Center, Shanghai 200051, China) Abstract: Exosomes are small membrane vesicles of endocytic origin that are secreted by many live cells. The specific functions of the different exosomes are correlated closely with the cell-specific proteins and the microenvironment of exosomes. Previous researches focus on the roles of exosome in stimulating and intensifying immunity. Recently, more and more studies show that exosomes can also down-regulate immune response or induce immune tolerance in specific environments. And especially more and more researchers pay attention to the roles of immune tolerance induced by exosomes in allotransplantation and autoimmune diseases. Therefore the applications for many diseases therapy through immune tolerance by exosomes will become a research hotspot. In this review we focus on exosomes biogenesis and the roles of induction of immune tolerance. Key words: exosomes; immunes tolerance; allotransplantation; autoimmune diseases; tumor immunity [1] exosome exosome (tumor-cell-derived exosome TEXs) DC exosome (dendritic-cell-derived exosome DEXs) exosome exosome 2006-08-14 2006-11-21 (0552nm010) (1982 )(1966 ) * Tel: 021-62957482 E-mail: fhh021@hotmail.com
2 exosome 175 exosome exosome 1 exosome exosome [1-3] [3] exosome (multivesicular bodys MVBs) [1] MVBs MVBs [1, 3] MVBs MVBs MVBs MVBs MHC-II MHC-II MVBs exosome MVBs [2-3] exosome MVBs Ca 2+ Stoorvogel [3] K562 exosomeca 2+ Clayton [4] Ca 2+ A23187 Burkil exosome exosome 2 exosome 2.1 exosome exosome 30 100 nm [1, 5] exosome 1.13 1.21 g/ml [1, 5] B exosome 60 80nm MVBs MVBs exosome [6] 2.2 exosome exosome Western blotting FACS exosome [1-3, 5-6] exosome exosome [5-6] ( ) (annexin rab ) ( G ) ( - 1) (Hsp70 Hsp84 Hsp90 ) exosome tetraspanins (CD9 CD63 CD81 CD82) [1,6] MHC exosome APC exosome [1] DEXs B exosome(bexs) MHC- II (CD86 CD80) T TEXs exosome LMP1 [5] T TEXs FasL AICD HLA-G [7] DEXs MFG-E8 [1,6,8] exosome DC DC T exosome A33 exosome P exosome N/CD13 [1,6] exosome BEXs
176 19 DEXs [6] 3 exosome exosome exosome [2] APC exosome MHC APC exosome DC exosome [1] exosome exosome exosome 3.1 (IECs)exosome Karlsson [9] exosome exosome Mallegol [10] IFN-γ IECs MODEK (OVA) IFN-γ OVA OVA IFN-γ exosome OVA IFN-γ exosome OVA Ostman [11] exosome( ) MHC 1983 Strobel [12] OVA 1h (DTH) OVA OVA IECs IECs 40 nm exosome MHC OVA OVA MHC IECs [9,11] SCID IECs MHC SCID IFN-γ IECs IFN-γ SCID IECs MHC IFN-γ MHC MHC [11] IECs MHC CD4 + T (Treg ) TGF-β IL-10 [5,9] Th1 CD4 + T 3.2 DC exosome(dexs) DC APC DC DC T [13] DEXs [14] DEXs Peche [15] BMDC DEXs( RT1u) DEXs(RT1a) 1 RT1u IFN-γ mrna 7 d 14 d 2 RT1u(1 10 25 100 µg) 10 µg DEXs [8] BMDC exosome LF15-0195 LF15-0195 DC DEXs
2 exosome 177 [16] Morelli [17] exosome exosomedc Kupffer DC exosome DC exosome CD8α DC CD8α + T MHC exosome CD4 + T exosome DC Kim [18] FasL DC DCFasL FasL DC exosome IL-10 BMDC IL-10 BMDC exosome [19] 3.3 exosome (TEXs) TEXs (TAA) APC T [20] TEXs CTL TEXs T [21-24] TEXs T Abusamra [21] FasL TEXs T TEXs TEXs FasL Fas T Fas Fas/FasL AICD T TEXs FasL T T [5] TEXs FasL [21] TEXs TEXs HLA-G [7] HLA-G NK CTL [5, 7] HLA-G exosome HLA-G TEXs TEXs EMP1 T Taylor Gercel-Talor [22] TEXs T CD3- JAK 3 T TEXs 3.4 exosome Frangsmyr [23] ( ) FasL exosome FasL exosome Fas [5] Waterhouse [24] exosome 17 CD9 Gansuvd [25] EB B exosome LMP1 CD4 + T (Treg ) T T exosome [2] 4 exosome
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