Department of Microbiology and Immunology, Virginia Commonwealth University, Massey Cancer Center, Richmond, VA 23298, USA.
Transplantation. 2012 May 15;93(9):949-57. doi: 10.1097/TP.0b013e3182497561.
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.
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) Vβs 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.
We identified three sets of T-cell clones that were either frequently involved in GVHD (TCR Vβ4, 11, and 23) or GVT effect (TCR Vβ9, 16, and 20), or were increased at the time of GVHD and GVT effects in a patient-specific manner (TCR Vβ2, 3, 7, 12, 15, and 17). Spectratyping analysis showed restricted clonality of the identified TCR Vβs. Polymerase chain reaction analysis also confirmed the presence of GVHD-associated T-cell clones at the site of the disease.
These data suggest that GVHD- and GVT-associated clones can be distinguished by molecular analysis of TCR Vβ to develop targeted therapy for GVHD.
在接受干细胞移植的血液恶性肿瘤患者中，供体的 T 细胞可以识别受者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，这种治疗的一个主要副作用是移植物抗宿主病（GVHD）。本研究的目的是描述频繁且仅涉及 GVHD 或移植物抗肿瘤（GVT）效应的独特 T 细胞克隆。
我们假设在疾病进展过程中可以识别出不同的 GVHD 相关 T 细胞克隆。为了验证这一点，我们使用定量逆转录聚合酶链反应和谱型分析，对 GVHD 患者与无 GVHD 和无复发存活患者的供体-受者对的 T 细胞受体（TCR）Vβ 进行了比较分析。
我们确定了三组 T 细胞克隆，它们要么频繁参与 GVHD（TCR Vβ4、11 和 23）或 GVT 效应（TCR Vβ9、16 和 20），要么在患者特异性的 GVHD 和 GVT 效应时增加（TCR Vβ2、3、7、12、15 和 17）。谱型分析显示鉴定出的 TCR Vβ 具有受限的克隆性。聚合酶链反应分析也证实了疾病部位存在与 GVHD 相关的 T 细胞克隆。
这些数据表明，通过 TCR Vβ 的分子分析可以区分 GVHD 和 GVT 相关克隆，从而为 GVHD 开发靶向治疗。
