TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

TCR spectratyping revealed T lymphocytes associated with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
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DOI:
10.1080/10428190701474357
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发表时间:
2007-01-01
影响因子:
2.6
通讯作者:
Zhu, Ping
Zhu, Ping
中科院分区:
医学4区
文献类型:
--
作者:
Du, Jin-Wei;Gu, Jiang-Ying;Zhu, Ping

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异基因造血干细胞移植(allo-HSCT)后 T 细胞的克隆扩增已被观察到,但其特征仍有待充分阐明。我们在此报告,CD8(+) T 细胞是所见的主要 T 淋巴细胞,并且在异基因 HSCT 后的前 3 个月内,T 细胞库多样性急剧下降。与非 GVHD 患者相比,II-IV 级 GVHD 患者的 T 细胞库多样性显着较低。 TCR β 可变基因 (TCRBV) 亚家族 8、5.1、5.2、4 和 13 是这些患者中扩展最频繁的 5 个亚家族。在鉴定的 49 个过度扩增克隆中,克隆型“TCR3-5”和“TCR18-5”是从 4 名具有 HLA-A2 等位基因和皮肤 GVHD 的患者中分离出来的。它们的频率与皮肤症状(即皮疹)密切相关。此外,在移植前,它们在供体中检测到,但在受体中未检测到。最后,发现了与GVHD相关的T细胞共有的三个常见的TCRBV CDR3基序:TGDS、GLAG和GGG。这些发现表明,TCR 谱型分析有助于揭示 GVHD 相关 T 细胞,并可能在早期诊断中发挥作用。
Clonal expansion of T cells after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been observed, but their characteristics remain to be fully elucidated. We report here that CD8(+) T cells were the dominant T lymphocytes seen and T-cell repertoire diversity decreased dramatically during the first 3 months after allo-HSCT. Patients with GVHD grade II-IV had significantly lower T-cell repertoire diversity compared with non-GVHD patients. TCR beta variable gene (TCRBV) subfamily 8, 5.1, 5.2, 4, and 13 were the five most frequently expanded subfamilies among these patients. Among the 49 over-expanded clones identified, clonotype "TCR3-5'' and "TCR18-5'' were isolated from four patients with HLA-A2 allele and skin GVHD. Their frequencies correlated well with skin symptoms (i. e. rash). Moreover, they were detected in donors but not detected in recipients before transplantation. Lastly, three common TCRBV CDR3 motifs shared by T cells related with GVHD were discovered: TGDS, GLAG, and GGG. These findings suggest that TCR spectratyping is helpful for revealing GVHD-related T cells and may have utility in early diagnosis.