Regulation of the epithelial cell-specific integrin, CD103, by human CD8+ cytolytic T lymphocytes

Regulation of the epithelial cell-specific integrin, CD103, by human CD8+ cytolytic T lymphocytes
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DOI:
10.1097/00007890-199906150-00005
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发表时间:
1999-06-15
期刊:
影响因子:
6.2
通讯作者:
Weir, MR
Weir, MR
中科院分区:
医学2区
文献类型:
--
作者:
Hadley, GA;Rostapshova, EA;Weir, MR

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背景CD 8(+)细胞溶解性T淋巴细胞(CTL)对移植物上皮的破坏是器官移植排斥反应的一个重要方面。我们最近在小鼠模型中发现,上皮细胞特异性整合素CD 103定义了CD 8(+)CTL的一个子集,这可能为这种相互作用提供了新的线索。本研究的目的是评估这些数据与人类系统的相关性,方法。结果:CD 103是混合淋巴细胞培养产生的CD 8(+)CTL的主要亚群(26-76%),细胞分选实验证实CD 103(+)和CD 103(-)亚群均具有同种特异性裂解活性。抗转化生长因子(TGF)-β阻断了CD 103(+)CTL亚群的出现,而CD 8(+)CTL持续表达CD 103依赖于具有生物活性的TGF-β。分离的CD 103(+)和CD 103(-)CD 8亚群在体外扩增过程中保持其表型完整性,尽管前者的最佳CD 103表达依赖于TGF-β。虽然在外周淋巴区室中活化的CD 8细胞中很少有CD 103(+)细胞,
Background. The destruction of the graft epithelium by CD8(+) cytolytic T lymphocytes (CTL) is an important aspect of organ allograft rejection. Our recent finding in a mouse model that the epithelial cell-specific integrin, CD103, defines a subset of CD8(+) CTL potentially sheds new light onto such interactions. The goal of the present study was to assess the relevance of these data to the human system,Methods. CD103 expression by human T-cell populations generated in mixed lymphocyte cultures or isolated from transplant nephrectomy specimens was quantitated using multiparameter FAGS analyses.Results, CD103 defined a major subset (26-76%) of CD8(+) CTL generated in human mixed lymphocyte cultures; cell sorting experiments confirmed that the CD103(+) and CD103(-) subsets both possess allospecific lytic activity. Anti-transforming growth factor (TGF)-beta blocked the appearance of the CD103(+) CTL subset, and persistent expression of CD103 by CD8(+) CTL was dependent on bioactive TGF-beta, Isolated CD103(+) and CD103(-) CD8 subsets maintained their phenotypic integrity during in vitro expansion, although optimal CD103 expression on the former was TGF-beta dependent. Although CD103(+) cells were rare among activated CD8 cells in peripheral lymphoid compartments (