Espada Eduardo, Cheng Matthew P, Kim Haesook T, Woolley Ann E, Avigan Jason I, Forcade Edouard, Soares Maria V D, Lacerda João F, Nikiforow Sarah, Gooptu Mahasweta, Romee Rizwan, Alyea Edwin P, Armand Philippe, Cutler Corey S, Ho Vincent T, Koreth John, Antin Joseph H, Soiffer Robert J, Marty Francisco M, Ritz Jerome
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
Blood Adv. 2020 May 12;4(9):1881-1893. doi: 10.1182/bloodadvances.2019001120.
Clinical disease caused by BK virus reactivation is a frequent complication of allogeneic hematopoietic cell transplantation (HCT). Because of the lack of effective antiviral agents, BK virus-specific T cells are emerging as a potential therapy for BK virus disease, but the immune response to BK virus after allogeneic HCT has not been well characterized. Our study describes reconstitution of BK virus-specific T-cell immunity in 77 adult patients after HCT. All patients had urinary symptoms, and urine was tested for BK virus replication; 33 patients were positive for BK virus (cases), and 44 were negative (controls). In BK virus cases, the median time to first positive test was 75 days (range, 2-511). BK virus cases had lower CD4 T-cell counts 3 to 9 months after transplant, but CD8 T-cell counts were similar in cases and controls. BK virus-specific T cells were identified by cytokine flow cytometry in cryopreserved samples collected prospectively. BK virus-specific CD4 T cells producing T helper 1 (Th1) cytokines recovered quickly after HCT. BK virus-specific T cells were detected more frequently in patients with BK virus reactivation at most time points, and CD4 T cells producing Th1 cytokines were more frequent than BK virus-specific cytolytic CD8 T cells. Early detection of interferon-γ+ and cytolytic BK virus-specific CD4 T cells was associated with lower rates of hematuria among cases. Overall, our study describes recovery of BK virus-specific T cells after HCT and the distinct roles for BK virus-specific T cells in the development and resolution of clinical symptoms.
BK病毒再激活引起的临床疾病是异基因造血细胞移植（HCT）常见的并发症。由于缺乏有效的抗病毒药物，BK病毒特异性T细胞正成为治疗BK病毒疾病的一种潜在疗法，但异基因HCT后对BK病毒的免疫反应尚未得到充分表征。我们的研究描述了77例成年患者HCT后BK病毒特异性T细胞免疫的重建情况。所有患者均有泌尿系统症状，并对尿液进行BK病毒复制检测；33例患者BK病毒检测呈阳性（病例组），44例呈阴性（对照组）。在BK病毒病例组中，首次检测呈阳性的中位时间为75天（范围为2 - 511天）。BK病毒病例组在移植后3至9个月时CD4 T细胞计数较低，但病例组和对照组的CD8 T细胞计数相似。通过细胞因子流式细胞术在预先采集的冷冻保存样本中鉴定BK病毒特异性T细胞。产生辅助性T细胞1（Th1）细胞因子的BK病毒特异性CD4 T细胞在HCT后迅速恢复。在大多数时间点，BK病毒再激活患者中BK病毒特异性T细胞的检测频率更高，且产生Th1细胞因子的CD4 T细胞比BK病毒特异性细胞毒性CD8 T细胞更常见。病例组中，早期检测到干扰素-γ+和细胞毒性BK病毒特异性CD4 T细胞与血尿发生率较低相关。总体而言，我们的研究描述了HCT后BK病毒特异性T细胞的恢复情况以及BK病毒特异性T细胞在临床症状发生和缓解中的不同作用。
