Analysis and application of anti-herpesviuses immunity among organ recipients by use of MHC-tetramers.

背景：器官接受者存在疱疹病毒感染的风险，包括巨细胞病毒（CMV）和EB病毒（EBV）。细胞毒性T细胞（CTL）是控制这些病毒感染的关键组分。四聚体HLA（tetramers）检测针对这些病毒的特异性CTL，并可能有助于未来的过继治疗，目的：评估四聚体作为监测CTL的试剂，并分离和扩增特异性CTL用于可能的治疗目的。所有人都有HLA A*0201或A*2402，相应的四聚体用于染色CTL。通过实时PCR监测病毒DNA。结果：A * 0201受体和A*2402受体的CMV感染频率相似，但A* 0201受体的CMV pp65四聚体比A* 2402受体的CMV pp65四聚体更有效地检测CTL。在存在CMV DNA血症的情况下，A*0201 CMV pp65四聚体在100%的受体中发现CTL，而A*2402 CMV pp65的情况下仅为46%。感染的严重程度是相似的，无论通过四聚体的CTL检测。类似的结果也得到了EBV。扩展的CTL失败，但CTL的数量较高时，病毒载量high.Interpretation：四聚体HLA检测只有一部分的整个抗病毒CTL，这使得它很难应用四聚体检测的CTL感染预后的预测。特异性CTL的分离失败的部分原因是缺乏合适的样品。对CMV感染的危险因素进行分析，为CMV感染的预后提供新的观点。

Background : Organ recipients are at risk of herpes viruses infection, including cytomegalovirus (CMV) and Epstein-Barr virus (EBV). Cytotoxic T-cells (CTL) are the pivotal component to control these viral infections. Tetrameric HLA (so-called tetramers) detect specific CTL against these viruses, and may help future adoptive therapy.Aim : To evaluate tetramers as agents for monitoring CTLs, and to isolate and expand specific CTL for possible therapeutic purpose.Methods : Sixty recipients of living liver graft were prospectively followed for 2-48 months. All had either of HLA A*0201 or A*2402, and corresponding tetramers were used to stain CTL. Viral DNA were monitored by real-time PCR. Samples with high viral load were assigned for isolation of specific CTLs by tetramers, and were incubated for expansion.Results : A*0201 CMV pp65 tetramer detected CTL more efficiently than A*2402 CMV pp65 tetramer, even though the frequency of CMV infection was similar in both of A*0201 recipients and A*2402 recipients. In the presence of CMV DNAemia, A*0201 CMV pp65 tetramer found CTL in 100% of recipients, whereas only 46% in case of A*2402 CMV pp65. Severity of infection was similar irrespective of CTL detection by tetramers. Similar results were obtained for EBV.Expansion of CTL failed although the amounts of CTL were higher when viral loads were high.Interpretation : Tetrameric HLA detects only a part of whole anti-viral CTL, which makes it difficult to apply tetramer detection of CTL for predictor of infection prognosis. Isolation of specific CTL failed partly due to scarcity of appropriate samples. An analysis of risk factors of CMV infection was done to add a new point of view for prognosis of infection.