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巨细胞病毒血清学阴性供体:对巨细胞病毒感染临床严重程度及巨细胞病毒特异性免疫重建的影响。

CMV seronegative donors: Effect on clinical severity of CMV infection and reconstitution of CMV-specific immunity.

作者信息

van der Heiden P L J, van Egmond H M, Veld S A J, van de Meent M, Eefting M, de Wreede L C, Halkes C J M, Falkenburg J H F, Marijt W A F, Jedema I

机构信息

Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.

Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.

出版信息

Transpl Immunol. 2018 Aug;49:54-58. doi: 10.1016/j.trim.2018.04.003. Epub 2018 Apr 18.

DOI:10.1016/j.trim.2018.04.003
PMID:29679650
Abstract

BACKGROUND

Cytomegalovirus (CMV)-specific T-cells are crucial to prevent CMV disease. CMV seropositive recipients transplanted with stem cells from a CMV seronegative allogeneic donor (RD) may be at risk for CMV disease due to absence of donor CMV-specific memory T-cells in the graft.

METHODS

We analyzed the duration of CMV reactivations and the incidence of CMV disease in RD and RD patients after alemtuzumab-based T-cell depleted allogeneic stem cell transplantation (TCD alloSCT). To determine the presence of donor-derived primary CMV-specific T-cell responses we analyzed the origin of CMV-specific T-cells in RD patients.

RESULTS

The duration of CMV reactivations (54 versus 38 days, respectively, p = 0.048) and the incidence of CMV disease (0.14 versus 0.02, p = 0.003 at 1 year after alloSCT) were higher in RD patients compared to RD patients. In RD patients, CMV-specific CD4 and CD8 T-cells were mainly of recipient origin. However, in 53% of RD patients donor-derived CMV-specific T-cells were detected within the first year.

CONCLUSIONS

In RD patients, immunity against CMV was predominantly mediated by recipient T-cells. Nevertheless, donor CMV serostatus significantly influenced the clinical severity of CMV reactivations indicating the role of CMV-specific memory T-cells transferred with the graft, despite the ultimate formation of primary donor-derived CMV-specific T-cell responses in RD patients.

摘要

背景

巨细胞病毒(CMV)特异性T细胞对于预防CMV疾病至关重要。接受来自CMV血清学阴性的异基因供体(RD)干细胞移植的CMV血清学阳性受者,可能因移植物中缺乏供体CMV特异性记忆T细胞而有患CMV疾病的风险。

方法

我们分析了基于阿仑单抗的T细胞清除异基因干细胞移植(TCD alloSCT)后RD和RD患者中CMV再激活的持续时间和CMV疾病的发生率。为了确定供体来源的原发性CMV特异性T细胞反应的存在,我们分析了RD患者中CMV特异性T细胞的来源。

结果

与RD患者相比,RD患者中CMV再激活的持续时间(分别为54天和38天,p = 0.048)和CMV疾病的发生率(alloSCT后1年时为0.14对0.02,p = 0.003)更高。在RD患者中,CMV特异性CD4和CD8 T细胞主要来源于受者。然而,在53%的RD患者中,在第一年就检测到了供体来源的CMV特异性T细胞。

结论

在RD患者中,针对CMV的免疫主要由受者T细胞介导。尽管如此,供体CMV血清状态显著影响了CMV再激活的临床严重程度,这表明尽管RD患者最终形成了原发性供体来源的CMV特异性T细胞反应,但移植时转移的CMV特异性记忆T细胞仍发挥了作用。

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