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健康供体和HIV-1感染者中TCR Vγ库的分析。

Analysis of the TCR Vgamma repertoire in healthy donors and HIV-1-infected individuals.

作者信息

Wesch D, Hinz T, Kabelitz D

机构信息

Department of Immunology, Paul-Ehrlich-Institute, Langen, Germany.

出版信息

Int Immunol. 1998 Aug;10(8):1067-75. doi: 10.1093/intimm/10.8.1067.

DOI:10.1093/intimm/10.8.1067
PMID:9723692
Abstract

During the course of infection with HIV-1, striking alterations in the subset distribution of peripheral blood gammadelta T cells are observed. While TCR Vdelta2 expression dominates among peripheral blood gammadelta T cells in healthy adults, there is a clear preponderance of Vdelta1 cells in HIV-1-infected persons. In this study, we present the first flow cytometry (FCM) analysis of the complete TCR Vgamma gene repertoire in HIV-1-infected individuals using a panel of mAb against all expressed Vgamma genes. The quantitative analysis of TCR Vgamma transcripts after amplification of cDNA by inverse PCR suggested that Vgamma5 usage is increased in HIV-1+ donors. This was confirmed by FCM with a new anti-Vgamma5 mAb. In addition, all members of the TCR VgammaI gene family (i.e. Vgamma2, 3, 4, 5 and 8) were expressed on significantly higher percentages of gammadelta T cells in HIV+ as compared to HIV- donors, whereas VgammaII (Vgamma9) expression was drastically reduced. No preferential association of the expanded Vdelta1+ cells with a particular Vgamma gene was observed in HIV-1 + donors. These results indicate that the increase in Vgamma1+ cells during HIV-1 infection occurs independently of the Vgamma gene usage and support the hypothesis that a Vdelta1-selective ligand might be involved.

摘要

在感染HIV-1的过程中,可观察到外周血γδT细胞亚群分布发生显著改变。在健康成年人的外周血γδT细胞中,TCR Vδ2表达占主导地位,而在HIV-1感染者中,Vδ1细胞明显占优势。在本研究中,我们使用一组针对所有表达的Vγ基因的单克隆抗体,首次对HIV-1感染者完整的TCR Vγ基因库进行了流式细胞术(FCM)分析。通过反向PCR扩增cDNA后对TCR Vγ转录本进行定量分析表明,HIV-1阳性供体中Vγ5的使用增加。这通过使用新型抗Vγ5单克隆抗体的流式细胞术得到了证实。此外,与HIV阴性供体相比,HIV阳性供体中γδT细胞上TCR VγI基因家族的所有成员(即Vγ2、3、4、5和8)的表达百分比显著更高,而VγII(Vγ9)的表达则大幅降低。在HIV-1阳性供体中未观察到扩增的Vδ1+细胞与特定Vγ基因有优先关联。这些结果表明,HIV-1感染期间Vγ1+细胞的增加独立于Vγ基因的使用,并支持可能涉及Vδ1选择性配体的假说。

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