Persistence of clonal T‐cell expansions following high‐dose chemotherapy and autologous peripheral blood progenitor cell rescue

Persistence of clonal T‐cell expansions following high‐dose chemotherapy and autologous peripheral blood progenitor cell rescue
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高剂量化疗和自体外周血祖细胞拯救后克隆 T 细胞扩增的持续性

DOI:
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发表时间:
2000
影响因子:
6.5
通讯作者:
A. Boylston
A. Boylston
中科院分区:
医学2区
文献类型:
--
作者:
A. Protheroe;C. Pickard;P. Johnson;T. Craddock;J. Shefta;K. Short;F. Lancaster;P. Selby;J. Henwood;A. Boylston

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利用自体外周血祖细胞救援(PBPCR)分析大剂量化疗后T淋巴细胞的再生可能有助于阐明免疫恢复的机制。采用流式细胞术分析接受大剂量化疗的成人患者治疗前后的T细胞受体可变β链(TCRBV)库。发现4例患者存在稳定的扩增(TCRBV3, 17, 21和22),范围从CD4+或CD8+库的8%到42%。我们证明,在这些患者中,在高剂量化疗和自体干细胞移植后,外周血中再次出现克隆扩增,并恢复到移植前水平。通过对TCR重排中的互补决定区(CDR)3部分的序列分析,进一步确定了三个扩增(CD3+CD8+TCRBV3+, CD3+CD4+TCRBV21+和CD3+CD8+TCRBV22+)。结果显示,这些细胞主要是克隆的,在PBPCR前后的外周血中发现了相同的序列,这证明了这些扩增中的绝大多数T细胞来自成熟淋巴细胞。该研究表明,接受自体PBPCR进行高剂量化疗的患者可再生克隆扩增,与预处理水平一致。他们还再生T细胞库,每个TCRBV家族代表的水平与高剂量化疗前相似。
Analysing the regeneration of T lymphocytes after high‐dose chemotherapy with autologous peripheral blood progenitor cell rescue (PBPCR) may help elucidate the mechanisms of immune recovery. The T‐cell receptor variable beta chain (TCRBV) repertoire of adult patients undergoing high‐dose chemotherapy was analysed by flow cytometry, before and after treatment. Four patients were found to have a stable expansion present (TCRBV3, 17, 21 and 22) ranging from 8% to 42% of the CD4+ or CD8+ repertoire. We demonstrated that, in these patients, following high‐dose chemotherapy and autologous stem cell transplantation, the clonal expansions reappeared in peripheral blood and returned to pretransplant levels. Three expansions (CD3+CD8+TCRBV3+, CD3+CD4+TCRBV21+ and CD3+CD8+TCRBV22+) were further defined by sequence analysis of the complementarity‐determining region (CDR)3 portion within the TCR rearrangements. These were shown to be predominantly clonal, with the same sequences being identified in peripheral blood before and after PBPCR, providing evidence that the overwhelming majority of T cells in these expansions arise from mature lymphocytes. This study demonstrated that patients undergoing autologous PBPCR for high‐dose chemotherapy regenerate clonal expansions, consistent with pretreatment levels. They also regenerate T‐cell repertoires with each TCRBV family represented to a similar level as that prior to high‐dose chemotherapy.
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正常个体和类风湿关节炎患者克隆 CD8 T 细胞扩增的分析。
DOI: --
发表时间: 1995
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
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