Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation

Involvement of mature donor T cells in the NK cell reconstitution after haploidentical hematopoietic stem-cell transplantation
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DOI:
10.1038/sj.leu.2405041
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发表时间:
2008-02
期刊:
影响因子:
11.4
通讯作者:
S. Nguyen;M. Kuentz;J. Vernant;N. Dhédin;D. Bories;P. Debré;V. Vieillard
S. Nguyen;M. Kuentz;J. Vernant;N. Dhédin;D. Bories;P. Debré;V. Vieillard
中科院分区:
医学1区
文献类型:
--
作者:
S. Nguyen;M. Kuentz;J. Vernant;N. Dhédin;D. Bories;P. Debré;V. Vieillard

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我们之前证明,单倍体干细胞移植(SCT)后产生的自然杀伤细胞(NK)在以表型特征和功能受损为特征的未成熟状态被阻断,这可能影响移植结果。我们假设移植物中缺乏成熟供体T细胞可能会影响NK细胞的分化。我们将21名接受部分(pTCD, n= 11)或广泛(eTCD, n= 10) t细胞消耗的移植受者的NK细胞与健康供者的NK细胞进行了比较。我们报道,尽管存在强烈的移植物抗宿主病(GvHD)反应,但在SCT期间存在T细胞的pTCD患者比eTCD移植患者具有更好的临床结果。此外,移植后pTCD患者的CD3−CD56 bright和NKG2A+ NK细胞的频率远低于eTCD患者,并且pTCD移植后对原发性单倍错配细胞的细胞毒性水平明显高于eTCD移植后的细胞毒性水平。这些发现强烈表明,在单倍体同种SCT后,移植物中的成熟供体T细胞可能在体内NK细胞分化中发挥关键作用。
We previously demonstrated that natural killer (NK) cells generated after haploidentical stem-cell transplantation (SCT) are blocked at an immature state characterized by phenotypic features and impaired functioning and that this may affect transplantation outcome. We hypothesize that the absence of mature donor T cells in the graft may affect NK cell differentiation. NK cells from 21 transplant recipients who underwent either partial (pTCD; n= 11) or extensive (eTCD; n= 10) T-cell depletion were compared with NK cells from their healthy donors. We report that despite the strong graft-versus-host disease (GvHD) reaction, pTCD patients, with T cells present during SCT, had a better clinical outcome than patients with eTCD transplants. In addition, the frequency of CD3− CD56 bright and NKG2A+ NK cells was much lower in pTCD than in eTCD patients after transplantation, and the level of cytotoxicity against primary haplo-mismatched blasts was significantly more pronounced after pTCD than eTCD transplants. These finding strongly suggest that mature donor T cells in the graft may play a key role in NK cell differentiation in vivo, after haploidentical SCT.