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NK细胞杀伤抑制受体(NK-KIR)转录动力学与异基因骨髓移植后急性移植物抗宿主病的发生相关。

NK-KIR transcript kinetics correlate with acute graft-versus-host disease occurrence after allogeneic bone marrow transplantation.

作者信息

Denis Laure, Gagne Katia, Gueglio Brigitte, Kerdudou Nolwenn, Milpied Noel, Simon Philippe, Follea Gilles, Bonneville Marc, Harousseau Jean-Luc, Bignon Jean-Denis

机构信息

HLA Laboratory, EFS Pays de Loire, Nantes, France.

出版信息

Hum Immunol. 2005 May;66(5):447-59. doi: 10.1016/j.humimm.2005.01.008. Epub 2005 Feb 19.

Abstract

Natural killer (NK) cell alloreactivity observed during stem cell transplantation (SCT) can be either beneficial (graft-versus-leukemia effect) or detrimental to the host (graft-versus-host disease). Killer immunoglobulin-like receptors (KIRs), expressed on NK and CD8 memory T cells, are regulated at a posttranscriptional level and, because there are currently no KIR-specific antibodies available, the analysis of these receptors remains elusive. To better define the role of cells expressing KIR after SCT, we studied KIR transcript repertoires in 29 grafted patients who received myeloablative or nonmyeloablative regimens. We restricted our analysis to 3DL1, 3DL2, 2DL4, 2DS3, and 2DS4 KIR transcripts 6 months after SCT. Absolute counts of NK and CD8 T cells were determined by flow cytometry, and KIR transcripts were quantified by real-time reverse transcription polymerase chain reaction at days 14, 28, 60, 100, and 180 after transplantation. Three groups of patients were identified. Groups I and III were characterized by the absence or a delayed appearance of KIR transcripts, which correlated with the highest risk of acute graft-versus-host disease (aGvHD). In contrast, in group II, a significant transcript peak was observed early, and only one patient suffered from aGvHD (p = 0.025). Thus determining the kinetics of KIR transcription should make it possible to identify transplanted patients at a high risk of developing aGvHD.

摘要

在干细胞移植(SCT)过程中观察到的自然杀伤(NK)细胞同种异体反应性对宿主可能有益(移植物抗白血病效应),也可能有害(移植物抗宿主病)。杀伤细胞免疫球蛋白样受体(KIR)在NK细胞和CD8记忆T细胞上表达,在转录后水平受到调控,并且由于目前没有KIR特异性抗体,对这些受体的分析仍然难以捉摸。为了更好地界定SCT后表达KIR的细胞的作用,我们研究了29例接受清髓或非清髓方案移植患者的KIR转录谱。我们将分析限制在SCT后6个月的3DL1、3DL2、2DL4、2DS3和2DS4 KIR转录本。通过流式细胞术确定NK细胞和CD8 T细胞的绝对计数,并在移植后第14、28、60、100和180天通过实时逆转录聚合酶链反应对KIR转录本进行定量。确定了三组患者。第一组和第三组的特征是KIR转录本缺失或出现延迟,这与急性移植物抗宿主病(aGvHD)的最高风险相关。相反,在第二组中,早期观察到一个显著的转录本峰值,只有一名患者患有aGvHD(p = 0.025)。因此,确定KIR转录的动力学应该能够识别出发生aGvHD高风险的移植患者。

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