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[从CD34+造血祖细胞获得的树突状细胞的体外分化及功能]

[In vitro differenciation and functions of dendritic cells obtained from CD34+ hematopoietic progenitors].

作者信息

Dubois B, Caux C

机构信息

Schering-Plough, Laboratory for Immunological Research, DARDILLY, France.

出版信息

Pathol Biol (Paris). 1995 Dec;43(10):829-40.

PMID:8786887
Abstract

Dendritic Cells (DC) are professional antigen presenting cells, necessary during the initiation of immune responses. The study of the role of DC in the establishment of this response has long been tempered by the difficulties to purify DC in sufficient numbers. In vitro generation of DC, from CD34+ hematopoietic progenitors in human and mice, should permit to clarify the relationships between the different DC types isolated in vivo and their roles. GM-CSF has been described to play a key role in the propagation of DC. In human, in association with TNF alpha, it allows the generation of DC from CD34+ progenitors. Those in vitro generated DC are capable of receptor mediated endocytosis and can present soluble antigen to specific T cell clones and activate naive T cells. During activation of naive T cells CD86 (on DC)--CD28 (on T lymphocyte) interaction seems to play a critical role. Interestingly, DC express a functional CD40, which triggering upregulates expression of CD80 and CD86 and induces cytokine production, indicating a reciprocal talk between DC and T cells during the course of antigen presentation. Finally, in vitro generated DC interact directly with B cells, activated through their CD40 antigen, leading to enhanced growth, differentiation (IgM production) and preferential isotype switch towards IgA. Thus, in the extrafollicular area of secondary lymphoid organs, in addition to prime naive T cells, DC might also directly provide costimulatory signals involved during the initiation of primary B cell responses.

摘要

树突状细胞(DC)是专职抗原呈递细胞,在免疫反应启动过程中必不可少。长期以来,由于难以获得足够数量的纯化DC,对DC在这种反应建立过程中作用的研究受到了限制。在人和小鼠中,从CD34 +造血祖细胞体外生成DC,应有助于阐明体内分离的不同DC类型之间的关系及其作用。GM-CSF已被描述在DC的增殖中起关键作用。在人类中,与TNFα联合使用时,它可使CD34 +祖细胞生成DC。这些体外生成的DC能够进行受体介导的内吞作用,并能将可溶性抗原呈递给特定的T细胞克隆并激活幼稚T细胞。在幼稚T细胞激活过程中,CD86(在DC上)-CD28(在T淋巴细胞上)的相互作用似乎起关键作用。有趣的是,DC表达功能性CD40,其触发可上调CD80和CD86的表达并诱导细胞因子产生,这表明在抗原呈递过程中DC与T细胞之间存在相互作用。最后,体外生成的DC通过其CD40抗原直接与活化的B细胞相互作用,导致生长增强、分化(产生IgM)以及优先向IgA的同种型转换。因此,在二级淋巴器官的滤泡外区域,除了激活幼稚T细胞外,DC还可能直接提供初级B细胞反应启动过程中涉及的共刺激信号。

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