Distinct Oligoclonal T Cells Are Associated With Graft Versus Host Disease After Stem-Cell Transplantation
Distinct Oligoclonal T Cells Are Associated With Graft Versus Host Disease After Stem-Cell Transplantation
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DOI：
10.1097/tp.0b013e3182497561
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发表时间：
2012-05-15
期刊：
影响因子：
6.2
通讯作者：
Manjili, Masoud H.
中科院分区：
文献类型：
--
作者：
Berrie, Jennifer L.;Kmieciak, Maciej;Manjili, Masoud H.
背景在接受干细胞移植的恶性血液病患者中，供体的T细胞可以识别受体细胞上的次要组织相容性抗原，并产生针对肿瘤的客观反应。然而，这种疗法的主要副作用是移植物抗宿主病（GVHD）。本研究的目的是描述不同的T细胞克隆，这些T细胞克隆经常和专门参与GVHD或移植物抗肿瘤（GVT）效应。我们假设，不同的GVHD相关的T细胞克隆可以在疾病进展过程中确定。为了验证这一点，我们采用定量逆转录聚合酶链反应和光谱分析法，对GVHD患者与无GVHD和无复发生存患者的供受者对T细胞受体（TCR）V β进行了比较分析。我们鉴定了三组T细胞克隆，它们要么经常参与GVHD（TCR V β 4、11和23）或GVT效应（TCR V β 9、16和20），要么在GVHD和GVT效应时以患者特异性方式增加（TCR V β 2、3、7、12、15和17）。光谱分析显示鉴定的TCR V β的克隆性受限。聚合酶链反应分析也证实了GVHD相关的T细胞克隆在疾病部位的存在。这些数据表明，GVHD和GVT相关的克隆可以区分TCR V β的分子分析，以开发GVHD的靶向治疗。
Background. In patients with hematologic malignancies who receive stem-cell transplantation, donors' T cells can recognize minor histocompatibility antigens on recipient cells and generate an objective response against the tumor. However, a major side effect of such therapy is graft-versus-host disease (GVHD). The purpose of this study was to characterize distinct T-cell clones that were frequently and exclusively involved in GVHD or graft-versus-tumor (GVT) effects.Methods. We hypothesized that distinct GVHD-associated T-cell clones can be identified during the disease progression. To test this, we conducted comparative analysis of T-cell receptor (TCR) V beta s in donor-recipient pairs of patients with GVHD versus those with GVHD-free and relapse-free survival using quantitative reverse-transcriptase polymerase chain reaction and spectratyping analyses.Results. We identified three sets of T-cell clones that were either frequently involved in GVHD(TCR V beta 4, 11, and 23) or GVT effect (TCR V beta 9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR V beta 2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR V beta s. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease.Conclusions. These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR V beta to develop targeted therapy for GVHD.