Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
J Clin Virol. 2011 May;51(1):31-7. doi: 10.1016/j.jcv.2011.01.014. Epub 2011 Mar 5.
In Japan, chronic active Epstein-Barr virus infection (CAEBV) may manifest with infection of T-cells or NK-cells, clonal lymphoid proliferations, and overt lymphoid malignancy. These EBV-positive lymphoproliferative disorders (EBV(+)LPD) of childhood are related to, but distinct from the infectious mononucleosis-like CAEBV seen in Western populations. The clonal nature of viral infection within lymphoid subsets of patients with EBV(+)LPD of childhood is not well described.
Viral distribution and clonotype were assessed within T-cell subsets, NK-cells, and CD34(+)stem cells following high purity cell sorting.
Six Japanese patients with EBV(+)LPD of childhood (3 T-cell LPD and 3 NK-cell LPD) were recruited. Prior to immunochemotherapy, viral loads and clonal analyses of T-cell subsets, NK-cells, and CD34(+)stem cells were studied by high-accuracy cell sorting (>99.5%), Southern blotting and real-time polymerase chain reaction.
Patient 1 had a monoclonal proliferation of EBV-infected γδT-cells and carried a lower copy number of EBV in αβT-cells. Patients 2 and 3 had clonal expansions of EBV-infected CD4(+)T-cells, and lower EBV load in NK-cells. Patients 4, 5 and 6 had EBV(+)NK-cell expansions with higher EBV load than T-cells. EBV-terminal repeats were determined as clonal bands in the minor targeted populations of 5 patients. The size of terminal repeats indicated the same clonotype in minor subsets as in the major subsets of four patients. EBV was not, however, detected in the bone marrow-derived CD34(+)stem cells of patients.
A single EBV clonotype may infect multiple NK-cell and T-cell subsets of patients with EBV(+)LPD of childhood. CD34(+)stem cells are spared, suggesting infection of more differentiated elements.
在日本，慢性活动性 EBV 感染（CAEBV）可能表现为 T 细胞或 NK 细胞感染、克隆性淋巴增生和明显的淋巴恶性肿瘤。这些儿童期 EBV 阳性淋巴增生性疾病（EBV(+)LPD）与西方人群中所见的传染性单核细胞增多症样 CAEBV 相关，但又有所不同。儿童期 EBV(+)LPD 患者的淋巴细胞亚群中病毒感染的克隆性质尚未得到很好的描述。
通过高纯度细胞分选评估 T 细胞亚群、NK 细胞和 CD34(+)干细胞内的病毒分布和克隆型。
招募了 6 例日本儿童期 EBV(+)LPD 患者（3 例 T 细胞 LPD 和 3 例 NK 细胞 LPD）。在免疫化学治疗之前，通过高精度细胞分选（>99.5%）、Southern 印迹和实时聚合酶链反应研究 T 细胞亚群、NK 细胞和 CD34(+)干细胞的病毒载量和克隆分析。
患者 1 存在 EBV 感染的 γδT 细胞单克隆增殖，αβT 细胞中 EBV 拷贝数较低。患者 2 和 3 存在 EBV 感染的 CD4(+)T 细胞克隆扩增，NK 细胞中 EBV 载量较低。患者 4、5 和 6 存在 EBV(+)NK 细胞扩增，EBV 载量高于 T 细胞。在 5 例患者的少数目标群体中，EBV 末端重复被确定为克隆带。末端重复的大小表明，在 4 例患者的次要亚群中存在相同的克隆型。然而，在患者的骨髓来源的 CD34(+)干细胞中未检测到 EBV。
单一 EBV 克隆型可能感染儿童期 EBV(+)LPD 患者的多个 NK 细胞和 T 细胞亚群。CD34(+)干细胞不受影响，提示感染了更分化的细胞。
