Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients.
Quantitative characterization of T-cell repertoire in allogeneic hematopoietic stem cell transplant recipients.
复制标题
同种异体造血干细胞移植受者中T细胞库的定量表征。
DOI：
10.1038/bmt.2015.133
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发表时间：
2015-09
影响因子：
4.8
通讯作者：
Nakamura Y
中科院分区：
文献类型：
--
作者：
Yew PY;Alachkar H;Yamaguchi R;Kiyotani K;Fang H;Yap KL;Liu HT;Wickrema A;Artz A;van Besien K;Imoto S;Miyano S;Bishop MR;Stock W;Nakamura Y
异基因造血干细胞移植（HSCT）是治疗恶性血液病的有效方法之一。尽管供者T淋巴细胞介导的GVHD仍然是allo-HSCT最具挑战性的毒性，但靶向白血病细胞的移植物抗白血病（GVL）效应在影响AML患者的总体结局中具有重要作用。在这里，我们使用下一代测序方法对接受匹配供体或单倍脐带HSCT的患者的TCR库进行了全面表征。我们的研究定义了每个TCRA和TCRB克隆的功能动力学，以及T细胞多样性的变化（鉴定了CDR 3序列）和某些T细胞的克隆扩增程度。使用这种方法，我们的研究表明，移植后30天的脐带血细胞的百分比较高，与TCR库的多样性较高，暗示了脐带嵌合体在增强免疫恢复中的作用。重要的是，我们发现GVHD和复发，彼此排斥，与较低的TCR库多样性和某些T细胞克隆的扩增相关。我们的研究结果突出了对GVHD和GVL效应之间平衡的新见解，表明移植后早期较高的多样性可能意味着HSCT移植后GVHD和复发的风险较低。
Allogeneic hematopoietic stem cell transplantation (HSCT) is one of curative treatment options for patients with hematologic malignancies. Although GVHD mediated by the donor's T lymphocytes remains the most challenging toxicity of allo-HSCT, graft-versus-leukemia (GVL) effect targeting leukemic cells, has an important role in affecting the overall outcome of patients with AML. Here we comprehensively characterized the TCR repertoire in patients who underwent matched donor or haplo-cord HSCT using next-generation sequencing approach. Our study defines the functional kinetics of each TCRA and TCRB clone, and changes in T-cell diversity (with identification of CDR3 sequences) and the extent of clonal expansion of certain T-cells. Using this approach, our study demonstrates that higher percentage of cord-blood cells at 30 days after transplant was correlated with higher diversity of TCR repertoire, implicating the role of cord-chimerism in enhancing immune recovery. Importantly, we found that GVHD and relapse, exclusive of each other, were correlated with lower TCR repertoire diversity and expansion of certain T-cell clones. Our results highlight novel insights into the balance between GVHD and GVL effect, suggesting that higher diversity early after transplant possibly implies lower risks of both GVHD and relapse following the HSCT transplantation.