Department of Histopathology, Hammersmith Hospital, Imperial College, London, UK.
Mod Pathol. 2011 Feb;24(2):232-40. doi: 10.1038/modpathol.2010.186. Epub 2010 Sep 10.
As has been previously shown, the lack of immune surveillance plays a major role in the unchecked proliferation of Epstein-Barr virus (EBV)-infected B cells in the pathogenesis of B-cell post-transplant lymphoproliferative disorders. We hypothesised that the lack of immune surveillance should possibly also affect T cells, and this should lead to subsequent emergence of T-cell clones. The presence of both B- and T-cell clones in post-transplant lymphoproliferative disorders samples has rarely been demonstrated in the past. We systematically evaluated 26 B-cell post-transplant lymphoproliferative disorder, 23 human immune deficiency virus-associated B-cell lymphoma and 10 immune-competent diffuse large B-cell lymphoma samples for B- and T-cell clonality (polymerase chain reaction and heteroduplex analysis using BIOMED-2 protocol), T-cell subsets (immunohistochemistry) and EBV association (in situ hybridisation using EBER). One-half of B-cell post-transplant lymphoproliferative disorders showed evidence of monoclonal T-cell expansion, and among the T cells present in the tissue samples, CD8-positive cells predominated. Although 9/13 (69%) B-cell post-transplant lymphoproliferative disorders with the presence of monoclonal T-cell population had a CD4:CD8 ratio of ≤0.4, 0/13 of the cases without monoclonal T-cell expansion had a ratio ≤0.4 (P = 0.002). Only 2/26 (8%) demonstrated significant cytological atypia in the CD3/CD8-positive cells. There was no association between EBV and presence of T-cell clones. T-cell clones were not identified in lymphomas other than B-cell post-transplant lymphoproliferative disorders. Among 53.8% cases of EBV-positive B-cell post-transplant lymphoproliferative disorders with associated clonal expansion of T-cells tested, none had EBV-positive T cells. We conclude that half of B-cell post-transplant lymphoproliferative disorders are associated with clonal expansion of CD8-positive T cells, most of which do not amount to the coexistence of a T-cell post-transplant lymphoproliferative disorders.
如前所述，免疫监视的缺失在 EBV 感染的 B 细胞在 B 细胞移植后淋巴组织增生性疾病发病机制中的不受控制的增殖中起着主要作用。我们假设免疫监视的缺失也可能影响 T 细胞，这将导致随后出现 T 细胞克隆。在过去，很少有研究证明移植后淋巴组织增生性疾病样本中存在 B 细胞和 T 细胞克隆。我们系统地评估了 26 例 B 细胞移植后淋巴组织增生性疾病、23 例人类免疫缺陷病毒相关 B 细胞淋巴瘤和 10 例免疫功能正常的弥漫性大 B 细胞淋巴瘤样本的 B 细胞和 T 细胞克隆性（聚合酶链反应和使用 BIOMED-2 方案的异源双链分析）、T 细胞亚群（免疫组织化学）和 EBV 相关性（原位杂交使用 EBER）。一半的 B 细胞移植后淋巴组织增生性疾病表现出单克隆 T 细胞扩增的证据，并且在组织样本中存在的 T 细胞中，CD8 阳性细胞占优势。尽管 9/13（69%）例 B 细胞移植后淋巴组织增生性疾病存在单克隆 T 细胞群体，但其中有 CD4:CD8 比值≤0.4 的病例为 0/13（P=0.002）。只有 2/26（8%）例在 CD3/CD8 阳性细胞中显示出明显的细胞学异型性。在没有单克隆 T 细胞扩增的病例中，没有发现 EBV 与 T 细胞克隆之间存在相关性。除了 B 细胞移植后淋巴组织增生性疾病外，其他淋巴瘤中均未发现 T 细胞克隆。在 53.8%经测试 EBV 阳性 B 细胞移植后淋巴组织增生性疾病中，其中与 T 细胞克隆性扩张相关的病例中，均没有 EBV 阳性 T 细胞。我们的结论是，一半的 B 细胞移植后淋巴组织增生性疾病与 CD8 阳性 T 细胞的克隆性扩张有关，其中大多数并不等同于 T 细胞移植后淋巴组织增生性疾病的共存。
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