The transcriptome of human cytotoxic T cells:: Similarities and disparities among allostimulated CD4+ CTL, CD8+ CTL and NK cells

The transcriptome of human cytotoxic T cells:: Similarities and disparities among allostimulated CD4+ CTL, CD8+ CTL and NK cells
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DOI:
10.1111/j.1600-6143.2007.02128.x
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发表时间:
2008-03-01
影响因子:
8.8
通讯作者:
Halloran, P. F.
Halloran, P. F.
中科院分区:
医学2区
文献类型:
--
作者:
Hidalgo, L. G.;Einecke, G.;Halloran, P. F.

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细胞毒性 T 淋巴细胞 (CTL) 中表达的转录本在移植中具有重要的机制和诊断意义。我们使用微阵列选择在人CD4(+)CTL、CD8(+)CTL和NK细胞中表达的CTL相关转录本(CAT),不包括在B细胞、单核细胞和肾脏中表达的转录本。这生成了三个转录本集:CD4(+) 相关、CD8(+) 相关和 NK 相关。令人惊讶的是,许多 CAT 在效应记忆细胞中表达,例如颗粒酶 B/GZMB、干扰素-γ/IFNG。 CD4(+) 和CD8(+) CTL 的转录表达非常相似。没有对CD4(+)CTL或CD8(+)CTL具有高度选择性的转录本:例如,细胞毒性分子转录本(穿孔素,颗粒酶,颗粒溶素)在CD8(+)CTL和CD4(+)CTL之间共享,尽管CD8(+)CTL中的表达仍然较高。区分CD8(+) CTL 和CD4(+) CTL 的转录本主要是CD8(+) CTL 和NK 细胞之间共享的转录本(例如NK 受体KLRC1、KLRC3、KLRD1、KLRK1)。没有转录本可以区分 CD4(+) CTL 和 CD8(+) CTL,但 NK 细胞相关转录本可以区分 NK 细胞和 CTL。这项研究为解释 CAT 在排斥同种异体移植物中的作用奠定了基础,并强调了 CAT 在 CD4(+) CTL、CD8(+) CTL 和效应记忆 T 细胞之间的广泛共享。
Transcripts expressed in cytotoxic T lymphocytes (CTL) have mechanistic and diagnostic importance in transplantation. We used microarrays to select CTL-associated transcripts (CATs) expressed in human CD4(+) CTL, CD8(+) CTL and NK cells, excluding transcripts expressed in B cells, monocytes and kidney. This generated three transcript sets: CD4(+)-associated, CD8(+)-associated and NK-associated. Surprisingly, many CATs were expressed in effector memory cells e.g. granzyme B/GZMB, interferon-gamma/IFNG. Transcript expression was very similar between CD4(+) and CD8(+) CTL. There were no transcripts highly selective for CD4(+) CTL or CD8(+) CTL: for example, cytotoxic molecule transcripts (perforin, granzymes, granulysin) were shared between CD8(+) CTL and CD4(+) CTL although expression remained higher in CD8(+) CTL. Transcripts that differentiated between CD8(+) CTL and CD4(+) CTL were primarily those shared between CD8(+) CTL and NK cells (e.g. NK receptors KLRC1, KLRC3, KLRD1, KLRK1). No transcripts could differentiate CD4(+) CTL from CD8(+) CTL but NK cell-associated transcripts could differentiate NK cells from CTL. This study serves as a foundation for the interpretation of CATs in rejecting allografts and highlights the extensive sharing of CATs among CD4(+) CTL, CD8(+) CTL and effector memory T cells.