Evidence that human CD8+CD45RA+CD27- cells are induced by antigen and evolve through extensive rounds of division

Evidence that human CD8+CD45RA+CD27- cells are induced by antigen and evolve through extensive rounds of division
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DOI:
10.1093/intimm/11.7.1027
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发表时间:
1999-07-01
影响因子:
4.4
通讯作者:
van Lier, RAW
van Lier, RAW
中科院分区:
医学3区
文献类型:
--
作者:
Hamann, D;Kostense, S;van Lier, RAW

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被引文献

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我们最近发现,循环的人类CD8(+)效应细胞具有CD45RA(+)CD27(-)膜表型,就其本身而言,这种表型似乎提出了一个悖论:CD45RA,一个由未引物细胞表达的标记,结合CD27的缺乏,这是慢性刺激T细胞的特征。为了研究向CD45RA(+)CD27(-)表型的分化是否依赖于抗原刺激并涉及细胞分裂,我们分析了不同外周血CD8(+)亚群中TCR v - β的使用和端粒限制性片段(TRF)长度。FAGS分析显示,CD8(+)CD45RA(+)CD27(+)细胞的TCR v - β库与未引物的CD8(+)CD45RA(+)CD27(+)细胞有显著差异。此外,在6个个体中的2个中,在CD8(+)CD45RA(+)CD27(-)亚群中观察到特定v - β家族的大量扩增。CDR3分型和单链确认分析表明,在CD8(+)CD45RA(+)CD27(-)群体中,22个测试的v - β家族大部分以寡克隆扩增为主,CD8(+)CD45RA(+)CD27(-)亚群的平均TRF长度比未引物的CD8(+)CD45RA(+)CD27(+)群体短2.3 +/- 1.0 kb,但与记忆型CD8(+)CD45RA(-)CD27(+) T细胞差异不大。这些发现表明,CD8(+)CD45RA(+)CD27(-)细胞毒性效应群体由抗原诱导的、克隆扩增的细胞组成,并证实CD45RA的表达并不是抗原非经历T细胞的严格标记。
We recently showed that circulating human CD8(+) effector cells have a CD45RA(+)CD27(-) membrane phenotype, In itself this phenotype appeared to pose a paradox: CD45RA, a marker expressed by unprimed cells, combined with absence of CD27, characteristic for chronically stimulated T cells. To investigate whether differentiation towards the CD45RA(+)CD27(-) phenotype is dependent on antigenic stimulation and involves cellular division, TCR V-beta usage and telomeric restriction fragment (TRF) length were analyzed within distinct peripheral blood CD8(+) subsets. FAGS analysis showed that the TCR V-beta repertoire of CD8(+)CD45RA(+)CD27(+) cells differed significantly from that of unprimed CD8(+)CD45RA(+)CD27(+) cells. Moreover, in two out of six individuals large expansions of particular V-beta families were observed in the CD8(+)CD45RA(+)CD27(-) subset. CDR3 spectrotyping and single-strand confirmation analysis revealed that within the CD8(+)CD45RA(+)CD27(-) population most of the 22 tested V-beta families were dominated by oligoclonal expansions, The mean TRF length was found to be 2.3 +/- 1.0 kb shorter in the CD8(+)CD45RA(+)CD27(-) subset compared with the unprimed CD8(+)CD45RA(+)CD27(+) population, but did not differ substantially from that of memory type, CD8(+)CD45RA(-)CD27(+) T cells. These findings indicate that the CD8(+)CD45RA(+)CD27(-) cytotoxic effector population consists of antigen-induced, clonally expanded cells and confirm that the expression of CD45RA is not a strict marker of antigen non-experienced T cells.