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
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Transpl Immunol. 2018 Aug;49:54-58. doi: 10.1016/j.trim.2018.04.003. Epub 2018 Apr 18.
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.
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.
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.
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.
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。
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。
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。
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。