Sester M, Sester U, Gärtner B, Heine G, Girndt M, Mueller-Lantzsch N, Meyerhans A, Köhler H
Medical Department IV, University of the Saarland, Homburg, Germany.
Transplantation. 2001 May 15;71(9):1287-94. doi: 10.1097/00007890-200105150-00018.
Immunosuppressive treatment in transplant patients frequently causes infectious complications with cytomegalovirus (CMV). The extent of CMV replication can be followed by a number of diagnostic methods. There is, however, no simple diagnostic tool to assess the quality of the cellular antiviral immune response of an individual patient. This would be of particular importance for therapy decisions, as patients with detectable virus load do not necessarily develop CMV-related disease. Using a rapid whole blood assay, the frequencies of CMV-reactive CD4 and CD8 T cells were followed after renal transplantation to characterize their relative contribution in the containment of CMV infection.
T cells from transplant patients ands healthy control persons were stimulated with CMV antigen in vitro. Based on specific cellular activation and induction of intracellular cytokines, the frequency of CMV-reactive CD4 and CD8 T cells was determined using flow cytometry. Viral load quantified using the "hybrid-capture" assay.
The absence of CMV complications in long-term transplant recipients is reflected by stable virus-specific T-cell frequencies, which do not differ from healthy CMV-positive controls. In contrast, during the first months after transplantation, clinical symptoms are preceded by a decrease in CMV-reactive CD4 T-cell frequencies and an increase in CMV load.
The individual immune response and CMV replication are critically balanced and can be characterized by assesing both viral load and antiviral T cells. Our experimental design allows the identification of patients with sufficient, insufficient, or absent T-cell activity and can serve as diagnostic tool to facilitate decisions on antiviral therapy.
移植患者的免疫抑制治疗经常引发巨细胞病毒(CMV)感染并发症。CMV复制程度可通过多种诊断方法进行跟踪。然而,目前尚无简单的诊断工具来评估个体患者细胞抗病毒免疫反应的质量。这对于治疗决策尤为重要,因为病毒载量可检测到的患者不一定会发生与CMV相关的疾病。通过一种快速全血检测方法,在肾移植后跟踪CMV反应性CD4和CD8 T细胞的频率,以确定它们在控制CMV感染中的相对作用。
体外使用CMV抗原刺激移植患者和健康对照者的T细胞。基于特异性细胞活化和细胞内细胞因子的诱导,使用流式细胞术测定CMV反应性CD4和CD8 T细胞的频率。使用“杂交捕获”检测法定量病毒载量。
长期移植受者中无CMV并发症表现为病毒特异性T细胞频率稳定,与健康的CMV阳性对照无差异。相反,在移植后的头几个月,临床症状出现之前,CMV反应性CD4 T细胞频率会下降,CMV载量会增加。
个体免疫反应与CMV复制处于关键平衡状态,可通过评估病毒载量和抗病毒T细胞来进行表征。我们的实验设计能够识别T细胞活性充足、不足或缺乏的患者,并可作为诊断工具以促进抗病毒治疗决策。