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STRUCTURE OF TCR ON TLYMPHOCYTES HARNESSING GRAFT-VERSUS-LEUKEMIA EFFECT

淋巴细胞 TCR 的结构利用移植物抗白血病效应

基本信息

批准号：
14570960
负责人：
HIROKAWA Makoto
金额：
$ 2.18万
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：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570960/
关键词：
T cell receptor Clone Allogeneic BMT Leukemia GVHD

项目摘要

We have found that recipients of allogeneic hematopoietic stem cell grafts have a skewing of the αβ TCR repertoire after transplant and this is a result of the proliferation of donor-derived mature T lymphocytes which can survive in recipients for several years. Expansion of the population of donor-derived TCRαβ+ T clones from a cytomegalovirus (CMV)-seropositive bone marrow donor was observed in a CMV-seropositive recipient when developing CMV-associated disease after transplantation. These results suggest that the clonal expansion of TCRαβ+ T cells and resulting skewed αβ TCR repertoire in peripheral blood following allogeneic hematopoietic stem cell transplantation (HSCT) primarily reflect the response to microorganisms. We have also found that stable clonal expansion of Vδ1+ _YδT lymphocytes persisted for several years after human allo-HSCT. CDR3 size spectratyping analysis revealed that twenty-three out of forty-two patients had highly skewed TCR repertoires of the Vδ1+ T cells. There was no apparent association between the oligoclonality of Vδ1+ TCRs and clinical outcome such as GVHD and leukemia relapse. In eight out of seventeen patients examined, the -WGI-amino acid sequence was observed in the CDR3 region of TCRs of clonally expanded Vδ1+ T cells. The -YWG-sequence was observed in four patients. All recipients examined were serologically positive for EBV-VCA IgG and EBNA. Autologous EBV transformed B cells could induce the expansion of Vδ1+ T cells. The CDR3 size distribution patterns of Vδ1+ TCRs became skewed after stimulation with autologous EBV-LCL, and the T cell clone with the -LEEYWGLPH-CDR3 sequence predominated in the culture with autologous EBV-LCL. These results suggest the CDR3 structure may contribute to recognition of EBV-associated antigens by Vδ1+ T cells. Skewing of the Vδ1+ TCR after allo-HSCT may be the result of the response to infectious antigens widely existing in humans such as EBV.

我们发现，异基因造血干细胞移植的受者在移植后αβTCR谱出现倾斜，这是供者来源的成熟T淋巴细胞增殖的结果，这些T淋巴细胞可以在受者体内存活数年。一例巨细胞病毒血清阳性的受者在移植后发生巨细胞病毒相关疾病时，观察到来自巨细胞病毒阳性骨髓供者的供体来源的αβ+T克隆的群体扩大。这些结果表明，异基因造血干细胞移植后外周血中αβ+T细胞的克隆性扩增和由此产生的偏斜的αβT细胞亚群主要反映了对微生物的应答。我们还发现Vδ1+_YδT淋巴细胞在人异基因造血干细胞移植后持续数年稳定克隆性扩增。CDR3型分析显示，2 3例患者的Vδ1+T细胞的TCR谱高度倾斜。V-δ-1+TCR的寡克隆性与移植物抗宿主病、白血病复发等临床结局之间无明显相关性。在17例患者中，有8例在克隆性扩增的Vδ1+T细胞的TCR的CDR3区观察到-WGI-氨基酸序列。在4名患者中观察到-YWG-序列。所有受检者的EBV-VCA、IgG和EBNA血清学检测均为阳性。自体EB病毒转化的B细胞可诱导Vδ1+T细胞的增殖。经自体EB病毒LCL刺激后，Vδ1+TCRs的CDR3大小分布模式发生扭曲，T细胞克隆中以-LEEYWGLPH-CDR3序列为主。这些结果提示CDR3结构可能有助于Vδ1+T细胞识别EB病毒相关抗原。异基因造血干细胞移植后Vδ1+TcR的偏斜可能是对广泛存在于人类中的感染性抗原(如EB病毒)的反应所致。

项目成果

期刊论文数量（30）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Codevelopment of dendritic cells along with erythroid differentiation from human CD34^+ cells by tumor necrosis factor-α.

树突状细胞的共同发育以及肿瘤坏死因子-α 从人类 CD34^+ 细胞中分化出的红细胞。

DOI：
发表时间：
2004
期刊：
Exp. Hematol 32(5)
影响因子：
0
作者：
Toyama-Sorimachi;N.;Y.toyoshima;Toyoshima Y;Koko Katagiri;Toyoshima Y;Kenji Kawada;Hiroshi Fukaya
通讯作者：
Hiroshi Fukaya

Hirokawa M., et al.: "Distinct TCRAV and TCRBV repertoire and CDR3 sequence of T lymphocytes clonally expanded in blood and GVHD lesions after human allogeneic bone marrow transplantation"Bone Marrow Transplantation. 30. 915-923 (2002)

Hirokawa M.等人：“人同种异体骨髓移植后，T淋巴细胞的不同TCRAV和TCRBV库以及CDR3序列在血液和GVHD病变中克隆扩增”骨髓移植。