Reconstitution of T cell receptor repertoire after human allogeneic bone marrow transplantation

人同种异体骨髓移植后 T 细胞受体库的重建

• 批准号: 08670508
• 负责人: HIROKAWA Makoto
• 金额: $ 1.34万
• 依托单位: Akita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670508/
• 关键词: marrow transplantation; T cell receptor; repertoire; CDR3; complications; T細胞; GVHD

Reconstitution of T cell receptor (TCR) repertoire after human allogeneic marrow transplantation was investigated. Informed consent was obtained before drawing blood samples from the patients and their marrow donors. TCR Vbeta and Valpha repertoire was analyzed by using adaptor ligation PCR and microplate hybridization assay techniques. There was no significant difference in TCR repertoire between donor-recipient. After8-10 weeks of transplant, a striking uncrease of the T cells carrying certain Vbeta and Valpha subfamilies was observed in all patients examined. Distorted TCR repertoire appears to retum to the normal pattem after 1 year of transplant. With the similar kinetics to the TCR repertoire changes, there was an increase of CD8+CD28-HLA-DR+T lymphocytes after transplant. Vbeta and Valpha chains with increased frequency were preferentially used in this lymphocyte subset. Taken together, the proliferation of CD8+CD28-HLA-DR+T lymphocytes results in the distortion of TCR repertoire after transplant.To investigate the TCR diversity of blood lymphocytes in marrow recipients, CDR3 size spectratyping analsis was also performed in several patients. The lack of multiple Vbeta subfamilies and the disturbed recovery of CDR3 complexity were observed in the patient with cytomegalovirus pneumonia, suggesting that this method might be useful for monitoring immune reconstitution after marrow transplantation.

研究了人同种异体骨髓移植后T细胞受体（TCR）库的重构。在抽取患者及其骨髓供者的血液样本前获得知情同意。采用接头连接PCR和微孔板杂交技术对TCR Vbeta和Valpha基因库进行分析。供者和受者在TCR全功能方面无显著差异。移植8-10周后，在所有检查的患者中观察到携带某些Vbeta和Valpha亚家族的T细胞显著增加。移植1年后，扭曲的TCR功能表恢复到正常模式。移植后CD8+CD28-HLA-DR+T淋巴细胞的增加与TCR库变化的动力学相似。频率增加的vβ和Valpha链优先用于该淋巴细胞亚群。综上所述，CD8+CD28-HLA-DR+T淋巴细胞的增殖导致移植后TCR库的扭曲。为了研究骨髓受者血液淋巴细胞TCR的多样性，我们还对几例患者进行了CDR3大小谱型分析。巨细胞病毒肺炎患者缺乏多个Vbeta亚家族，CDR3复杂性恢复紊乱，提示该方法可用于监测骨髓移植后的免疫重建。

项目成果

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