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来自巨细胞病毒特异性T细胞频率高的儿科供体的骨髓移植。

Bone marrow transplantation from a pediatric donor with a high frequency of cytomegalovirus-specific T-cells.

作者信息

Komatsu Haruki, Kogawa Kazuhiro, Nonoyama Shigeaki, Inui Ayno, Sogo Tsuyoshi, Fujisawa Tomoo, Klenerman Paul

机构信息

Department of Pediatrics, Sakura Hospital, Toho University, Chiba, Japan.

出版信息

J Med Virol. 2006 Dec;78(12):1616-23. doi: 10.1002/jmv.20746.

DOI:10.1002/jmv.20746
PMID:17063516
Abstract

A recent study reported that quantitation of cytomegalovirus (CMV)-specific CD8+ T lymphocytes in the graft and monitoring of these T cells might identify hematopoietic stem cell transplantation-recipients at the risk for progressive CMV infection. A 6-year-old girl underwent bone marrow transplantation from an HLA-identical sibling with a very high frequency of CMV specific tetramer-positive CD8+ T-cells. CMV-specific T-cell immunity was prospectively evaluated using a peptide (HLA-A2, NLVPMVATV). Tetramer assay showed that the frequency of CMV-specific CD8+ T cells of the donor in the peripheral blood was 5.3%, higher than average amongst young children. The frequency of CMV-specific CD8+ T cells of the donor in the graft was 3.7% of CD8+ T-cells. Before transplantation, the frequency of CMV specific CD8+ T cells of the recipient was 0.1% in the peripheral blood. Surprisingly, the frequency of CMV specific CD8+ T cells increased up to 30% of CD8+ T-cells at day 27 after transplantation. IFN-gamma enzyme-linked immunospot assay showed the recipient-T cells had strong responses to the A2-specific NLVPMVATV peptide. Although the phenotypic pattern of the CMV-specific T cells of the recipient was different from those of the donor before transplantation, the phenotype of the donor-derived cells retained their original phenotype in the recipient after transplantation. These finding suggested that active transferred immunity from the graft with a high frequency of CMV-specific CTL could induce a rapid reconstitution of CMV-specific T-cell mediated immunity in pediatric HLA-identical allogenetic bone marrow transplantation. The screening of peripheral blood using HLA-peptide tetramer staining might be beneficial to select donors.

摘要

最近一项研究报告称,对移植物中巨细胞病毒(CMV)特异性CD8 + T淋巴细胞进行定量分析并监测这些T细胞,可能会识别出有进行性CMV感染风险的造血干细胞移植受者。一名6岁女孩接受了来自人类白细胞抗原(HLA)匹配同胞的骨髓移植,其CMV特异性四聚体阳性CD8 + T细胞频率非常高。使用一种肽(HLA - A2,NLVPMVATV)对CMV特异性T细胞免疫进行了前瞻性评估。四聚体分析显示,供体外周血中CMV特异性CD8 + T细胞的频率为5.3%,高于幼儿的平均水平。移植物中供体CMV特异性CD8 + T细胞的频率为CD8 + T细胞的3.7%。移植前,受者外周血中CMV特异性CD8 + T细胞的频率为0.1%。令人惊讶的是,移植后第27天,CMV特异性CD8 + T细胞的频率增加到CD8 + T细胞的30%。干扰素 - γ酶联免疫斑点分析显示,受者T细胞对A2特异性NLVPMVATV肽有强烈反应。尽管移植前受者CMV特异性T细胞的表型模式与供体不同,但移植后供体来源细胞的表型在受者体内保留了其原始表型。这些发现表明,在儿科HLA匹配的同种异体骨髓移植中,具有高频率CMV特异性细胞毒性T淋巴细胞(CTL)的移植物产生的主动转移免疫可诱导CMV特异性T细胞介导的免疫快速重建。使用HLA - 肽四聚体染色对外周血进行筛查可能有助于选择供体。

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