Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
Transplantation. 2013 Jan 15;95(1):247-55. doi: 10.1097/TP.0b013e318279968d.
Posttransplantation lymphoproliferative disease (PTLD) is an often Epstein-Barr virus (EBV)-associated mainly malignant complication after transplantation. We present data on EBV-specific T cells in children treated with rituximab with or without chemotherapy on the pediatric PTLD Pilot 2005 protocol.
Peripheral blood mononuclear cells were isolated from 16 pediatric patients with PTLD, 4 transplanted children with EBV reactivation, and 18 healthy controls. EBV-specific T cells were quantified by flow cytometric detection of intracellular interferon-γ after stimulation with autologous EBV-transformed lymphoblastoid cell lines and correlated with EBV load in peripheral blood.
At diagnosis, PTLD patients had similar numbers of EBV-specific CD4 and CD8 T cells as healthy EBV-positive controls. EBV-specific T cells tended to be lower in early PTLD compared with late PTLD. During treatment with rituximab, CD4 and/or CD8 EBV-specific T cells increased in most patients, possibly reflecting restored immunocompetence due to a reduction of immunosuppression as well as antigenic stimulation by cross-presentation of EBV antigen from destroyed B cells. However, this increase did not predict response to rituximab or chemotherapy. EBV load and circulating B cells became undetectable in most patients during rituximab therapy. B-cell recovery after treatment was accompanied by redetection of EBV in peripheral blood, which was controlled by T-cell responses in 11 of 11 evaluable cases.
In pediatric PTLD patients, pretreatment EBV-specific T-cell numbers are in the range of healthy controls. These cells increased on reduction of immunosuppression and treatment with rituximab. Recurrence of EBV viremia during complete remission is matched by strong T-cell responses.
移植后淋巴组织增生性疾病（PTLD）是一种常与 EBV（Epstein-Barr virus）相关的主要恶性并发症，发生于移植后。我们报告了根据儿科 PTLD 2005 方案，在接受利妥昔单抗联合或不联合化疗的儿童中 EBV 特异性 T 细胞的数据。
从 16 例 PTLD 患儿、4 例 EBV 再激活的移植患儿和 18 例健康对照者的外周血单个核细胞中分离出外周血单个核细胞。通过流式细胞术检测自体 EBV 转化的淋巴母细胞系刺激后细胞内干扰素-γ，对 EBV 特异性 T 细胞进行定量，并与外周血 EBV 载量相关联。
在诊断时，PTLD 患者的 EBV 特异性 CD4 和 CD8 T 细胞数量与健康 EBV 阳性对照者相似。早期 PTLD 患者的 EBV 特异性 T 细胞数量趋于低于晚期 PTLD 患者。在利妥昔单抗治疗期间，大多数患者的 CD4 和/或 CD8 EBV 特异性 T 细胞增加，这可能反映了由于免疫抑制的减少以及被破坏的 B 细胞交叉呈递 EBV 抗原的抗原刺激而恢复了免疫功能。然而，这种增加并不能预测利妥昔单抗或化疗的反应。在大多数患者中，利妥昔单抗治疗期间 EBV 载量和循环 B 细胞变得不可检测。治疗后 B 细胞恢复时，外周血中再次检测到 EBV，在 11 例可评估病例中，有 11 例通过 T 细胞反应得到控制。
在儿科 PTLD 患者中，预处理 EBV 特异性 T 细胞数量在健康对照者范围内。这些细胞在减少免疫抑制和利妥昔单抗治疗时增加。完全缓解期间 EBV 病毒血症的复发与强烈的 T 细胞反应相匹配。
