Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation
Favorable impact of natural killer cell reconstitution on chronic graft-versus-host disease and cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation
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DOI：
10.3324/haematol.2014.108407
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发表时间：
2014-12-01
期刊：
影响因子：
10.1
通讯作者：
Moins-Teisserenc, Helesne
中科院分区：
文献类型：
--
作者：
Kheav, Vissal David;Busson, Marc;Moins-Teisserenc, Helesne
自然杀伤细胞是第一个重建的淋巴细胞亚群，在异基因造血干细胞移植后的早期免疫中发挥重要作用。表达激活受体NKG2C的细胞似乎对巨细胞病毒发作的解决至关重要，即使在没有T细胞的情况下也是如此。我们前瞻性地研究了2005至2012年间接受非T细胞耗竭异基因造血干细胞移植的439例成人受者的自然杀伤细胞重建。分别于移植后3、6、12、24个月采集新鲜血样进行分析。研究的数据涉及预适应方案、干细胞来源、潜在疾病、移植物抗宿主病的发生以及巨细胞病毒重新激活的情况。多因素分析发现，清髓性预适应后3个月CD56(明亮)自然杀伤细胞绝对数明显高于减强度预适应后。急性移植物抗宿主病损害了3个月时总自然杀伤细胞和CD56(DIM)自然杀伤细胞的重建。相反，3个月时自然杀伤细胞计数高与慢性移植物抗宿主病的发生率较低有关，与先前的急性移植物抗宿主病和干细胞来源无关。巨细胞病毒复活患者3个月时NKG2C(+)、CD56(DIM)和自然杀伤细胞总数在0~3个月间较低，但以后显著增加。在第3个月到第6个月期间经历巨细胞病毒重新激活的患者中，这些细胞的数量也较少。我们的结果支持表达NKG2C的自然杀伤细胞在异基因造血干细胞移植后早期控制巨细胞病毒重新激活中的直接作用。
Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T cells. We prospectively investigated natural killer-cell reconstitution in a cohort of 439 adult recipients who underwent non-T-cell-depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of graft-versus-host disease, and profiles of cytomegalovirus reactivation. In multivariate analysis we found that the absolute numbers of CD56(bright) natural killer cells at month 3 were significantly higher after myeloablative conditioning than after reduced intensity conditioning. Acute graft-versus-host disease impaired reconstitution of total and CD56(dim) natural killer cells at month 3. In contrast, high natural killer cell count at month 3 was associated with a lower incidence of chronic graft-versus-host disease, independently of a previous episode of acute graft-versus-host disease and stem cell source. NKG2C(+)CD56(dim) and total natural killer cell counts at month 3 were lower in patients with reactivation of cytomegalovirus between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced later cytomegalovirus reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.