Al-Talib Mohammed, Skaria Anna, Griffin Siân
Systems Immunity Research Institute, Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, UK.
Bristol Medical School, University of Bristol, Bristol, UK.
Transpl Infect Dis. 2025 Jan-Feb;27(1):e14401. doi: 10.1111/tid.14401. Epub 2024 Nov 5.
BK polyomavirus (BKPyV) is an important opportunistic viral infection that complicates kidney transplantation. Uncontrolled viral replication may result in BKPyV-associated nephropathy (BKPyVAN), a major cause of premature allograft damage and failure. In the continued absence of proven treatments, management relies on the empirical reduction of immunosuppression to facilitate an effective host immune response to clear the virus. This may be complicated by the risk of allograft rejection. There is compelling evidence that cellular immune responses are key to establishing control after viral reactivation. Measurable peripheral BKPyV-specific T cell responses temporally correlate with declining viral loads and subsequent clearance. Conversely, these responses are delayed or absent in BKPyVAN. How these peripheral findings correspond to the intragraft response, and whether BKPyV-specific T cells contribute to the immunopathology of BKPyVAN, remains poorly understood. Molecular techniques have provided some insights; however, these have been unable to fully discriminate BKPyVAN from cellular rejection to date. Furthermore, the contributions of components of innate cellular immunity, such as natural killer cells, are not known. Herein, we review the role of cellular immunity in BKPyV infection in kidney transplant recipients. We discuss advances in the understanding of how the development, phenotype, and functionality of these responses may determine the balance between viral control and immunopathology, and how this knowledge is being translated into tools to prognosticate and guide individualized immunosuppression reduction. Lastly, we consider how further elucidation of these responses may inform the design of therapies that would revolutionize how BKPyV is managed after transplantation.
BK多瘤病毒（BKPyV）是一种重要的机会性病毒感染，会使肾移植复杂化。病毒复制不受控制可能导致BK多瘤病毒相关性肾病（BKPyVAN），这是移植肾过早损伤和衰竭的主要原因。在仍然缺乏经证实的治疗方法的情况下，管理措施依赖于经验性降低免疫抑制，以促进有效的宿主免疫反应来清除病毒。这可能因移植肾排斥反应的风险而变得复杂。有令人信服的证据表明，细胞免疫反应是病毒重新激活后建立控制的关键。可测量的外周血BKPyV特异性T细胞反应在时间上与病毒载量下降及随后的清除相关。相反，这些反应在BKPyVAN中延迟出现或不存在。这些外周血的发现如何与移植肾内的反应相对应，以及BKPyV特异性T细胞是否促成BKPyVAN的免疫病理学，目前仍知之甚少。分子技术已经提供了一些见解；然而，迄今为止，这些技术尚无法完全区分BKPyVAN与细胞排斥反应。此外，先天性细胞免疫成分（如自然杀伤细胞）的作用尚不清楚。在此，我们综述细胞免疫在肾移植受者BKPyV感染中的作用。我们讨论了在理解这些反应的发生发展、表型和功能如何决定病毒控制与免疫病理学之间的平衡方面取得的进展，以及这些知识如何转化为预测和指导个体化免疫抑制降低的工具。最后，我们考虑进一步阐明这些反应如何为治疗方案的设计提供信息，从而彻底改变移植后BKPyV的管理方式。
