Direct stimulation of T cells by membrane vesicles from antigen-presenting cells
Direct stimulation of T cells by membrane vesicles from antigen-presenting cells
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DOI：
10.1073/pnas.0603466103
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发表时间：
2006-08-01
影响因子：
11.1
通讯作者：
Sprent, Jonathan
中科院分区：
文献类型：
--
作者：
Kovar, Marek;Boyman, Onur;Sprent, Jonathan
初始T细胞的活化通常需要T细胞受体介导的与活的抗原呈递细胞如树突状细胞（DC）上的MHC结合肽的接触。这里的证据表明，解离的细胞膜片段从DC线可以被用作一个有效的替代品的可行的DC。源自IFN-γ成熟DC的超声处理物的超浓缩材料富集在非常类似于外来体的小膜囊泡中。当与MHC I类限制性特异性肽复合时，来自DC超声处理物的囊泡在体外在不存在正常抗原呈递细胞的情况下通过纯化的幼稚CD 8（+）细胞产生强烈的应答，并且还可以有效地引发T细胞用于体内肿瘤排斥。在DC的总产量和相对免疫原性方面，来自DC超声处理物的膜囊泡比经典的外泌体有效得多，并且可能是肿瘤免疫治疗的有价值的工具。
Activation of naive T cells generally requires T cell receptor-mediated contact with MHC-bound peptides on viable antigen-presenting cells such as dendritic cells (DC). Here evidence is presented that dissociated cell membrane fragments from a DC line can be used as an effective substitute for viable DC. Ultracentrifuged material derived from sonicates of IFN-gamma-matured DC is enriched in small membrane vesicles that closely resemble exosomes. When complexed with MHC class I-restricted specific peptide, vesicles from DC sonicates generate strong responses by purified naive CD8(+) cells in vitro in the absence of normal antigen-presenting cells and can also efficiently prime T cells for tumor rejection in vivo. Both in terms of total yields from DC and relative immunogenicity, membrane vesicles from DC sonicates are much more effective than classic exosomes and may be a valuable tool for tumor immunotherapy.