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β7(βp)整合素在小鼠淋巴细胞上的表达与调控:与黏膜免疫系统的相关性

Expression and regulation of beta 7(beta p) integrins on mouse lymphocytes: relevance to the mucosal immune system.

作者信息

Kilshaw P J, Murant S J

机构信息

AFRC Institute of Animal Physiology and Genetics Research, Department of Cell Biology, Babraham, Cambridge, GB.

出版信息

Eur J Immunol. 1991 Oct;21(10):2591-7. doi: 10.1002/eji.1830211041.

Abstract

A mouse lymphocyte surface molecule which is selectively expressed by mucosal T cells and detected with the monoclonal antibody (mAb) M290 has provisionally been identified as a beta 7 integrin. Identification was based on close homology of its beta subunit at the N terminus with the recently reported, highly distinctive, human beta 7 sequence. mAb were prepared against the beta and alpha subunits of the mouse molecule, termed beta 7 and alpha M290, respectively, and used to study surface expression of the two components. beta 7 was present on most lymph node lymphocytes in association with alpha 4 rather than alpha M290. This integrin, beta 7 alpha 4, was shown to be identical to LPAM-1 (beta p alpha 4) the Peyer's patch homing receptor. Stimulation in vitro of mouse lymph node T cells with anti-CD3 in the presence of transforming growth factor (TGF)-beta increased beta 7 expression in about 40% of cells and changed the associated alpha chain from alpha 4 to the novel alpha M290 subunit, which, in most cells, was expressed de novo. Immunoprecipitation of beta 7 both from these cells and from intraepithelial lymphocytes gave closely similar results and showed predominance of the beta 7 alpha M290 integrin. It is suggested that in vivo this change in alpha-chain usage occurs in mucosal T cells in response to TGF-beta acting in the mucosal microenvironment and that the new integrin confers particular adhesive properties, possibly homing specificity, on the cells.

摘要

一种由黏膜T细胞选择性表达、可被单克隆抗体(mAb)M290检测到的小鼠淋巴细胞表面分子,已初步鉴定为β7整合素。鉴定依据是其β亚基N端与最近报道的高度独特的人β7序列具有高度同源性。制备了分别针对小鼠分子的β亚基和α亚基(分别称为β7和αM290)的单克隆抗体,并用于研究这两种成分的表面表达。β7存在于大多数淋巴结淋巴细胞上,与α4而非αM290结合。这种整合素β7α4被证明与派尔集合淋巴结归巢受体LPAM-1(βpα4)相同。在转化生长因子(TGF)-β存在的情况下,用抗CD3体外刺激小鼠淋巴结T细胞,约40%的细胞中β7表达增加,并且与之相关的α链从α4变为新的αM290亚基,在大多数细胞中,该亚基是从头表达的。从这些细胞和上皮内淋巴细胞中免疫沉淀β7得到了非常相似的结果,并显示β7αM290整合素占优势。有人提出,在体内,α链使用的这种变化发生在黏膜T细胞中,以响应黏膜微环境中TGF-β的作用,并且新的整合素赋予细胞特定的黏附特性,可能是归巢特异性。

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