Department of Nephrology, Charite University Medicine Berlin, Campus Virchow Clinic, Berlin, Germany.
Transplantation. 2011 Jan 15;91(1):100-7. doi: 10.1097/tp.0b013e3181fe1335.
Polyomavirus BK virus (BKV) infection represents a serious complication leading to BKV-associated nephropathy (BKVAN) and subsequent kidney graft loss in up to 10% of transplant patients. Cellular immunity is known to play a crucial role in the control of BKV replication. However, the knowledge on the BKV-T-cell response is limited: only two (VP1 and large T antigen) of six known BKV proteins were evaluated for their antigenicity so far.
By using 10-color flow cytometry and newly created overlapping peptide pools of five BKV antigens (VP1, VP2, VP3, large T antigen, and small t antigen), we performed cross-sectional phenotypic and functional analysis of BKV-specific T cells in kidney transplant patients with a history of BKVAN. Patients with clinically unapparent BKV infection (history of transient/no BKV reactivation) were used as control group.
Our data demonstrate for the first time the antigenic properties of all five evaluated proteins with VP3 as a new important target of cellular immunity. Further, we found a correlation between the severity of the previous BKV infection and the magnitude of memory CD4+ T-cell response. Thus, compared with the control group, patients with a history of BKVAN demonstrated significantly higher frequencies of interferon-γ- and interleukin-2-producing effector memory CD4+ T cells. In the control group, more patients with detectable interferon-γ+/interleukin-2+/tumor necrosis factor+ triple producers were found, suggesting possibly a protective function of these multifunctional T cells.
In conclusion, our study results suggest an implementation of new targets for monitoring of BKV immunity. Further studies are required to evaluate the protective function of the found BKV-specific T-cell subsets.
多瘤病毒 BK 病毒（BKV）感染是导致多达 10%的移植患者发生 BKV 相关肾病（BKVAN）和随后的肾移植物丢失的严重并发症。细胞免疫被认为在控制 BKV 复制中起着至关重要的作用。然而，目前对 BKV-T 细胞反应的了解有限：迄今为止，仅评估了六个已知 BKV 蛋白中的两个（VP1 和大 T 抗原）的抗原性。
通过使用 10 色流式细胞术和新创建的五个 BKV 抗原（VP1、VP2、VP3、大 T 抗原和小 t 抗原）的重叠肽池，我们对有 BKVAN 病史的肾移植患者进行了 BKV 特异性 T 细胞的横断面表型和功能分析。将有临床无明显 BKV 感染（有一过性/无 BKV 再激活病史）的患者作为对照组。
我们的数据首次证明了所有五个评估蛋白的抗原特性，其中 VP3 是细胞免疫的一个新的重要靶标。此外，我们发现先前 BKV 感染的严重程度与记忆性 CD4+T 细胞反应的幅度之间存在相关性。因此，与对照组相比，有 BKVAN 病史的患者表现出更高频率的干扰素-γ和白细胞介素-2 产生效应记忆 CD4+T 细胞。在对照组中，发现更多具有可检测的干扰素-γ+/白细胞介素-2+/肿瘤坏死因子+三阳性的患者，这表明这些多功能 T 细胞可能具有保护功能。
总之，我们的研究结果表明可以实施新的 BKV 免疫监测目标。需要进一步研究来评估发现的 BKV 特异性 T 细胞亚群的保护功能。
