Bharti Reena, Calabrese Daniel R
Department of Medicine, University of California, San Francisco, San Francisco, CA, United States.
Department of Medicine, San Francisco Veterans Affairs Medical Center, San Francisco, CA, United States.
Front Transplant. 2024 Jun 10;3:1388393. doi: 10.3389/frtra.2024.1388393. eCollection 2024.
Up to 90% of the global population has been infected with cytomegalovirus (CMV), a herpesvirus that remains latent for the lifetime of the host and drives immune dysregulation. CMV is a critical risk factor for poor outcomes after solid organ transplant, though lung transplant recipients (LTR) carry the highest risk of CMV infection, and CMV-associated comorbidities compared to recipients of other solid organ transplants. Despite potent antivirals, CMV remains a significant driver of chronic lung allograft dysfunction (CLAD), re-transplantation, and death. Moreover, the extended utilization of CMV antiviral prophylaxis is not without adverse effects, often necessitating treatment discontinuation. Thus, there is a critical need to understand the immune response to CMV after lung transplantation. This review identifies key elements of each arm of the CMV immune response and highlights implications for lung allograft tolerance and injury. Specific attention is paid to cellular subsets of adaptive and innate immune cells that are important in the lung during CMV infection and reactivation. The concept of heterologous immune responses is reviewed in depth, including how they form and how they may drive tissue- and allograft-specific immunity. Other important objectives of this review are to detail the emerging role of NK cells in CMV-related outcomes, in addition to discussing perturbations in CMV immune function stemming from pre-existing lung disease. Finally, this review identifies potential mechanisms whereby CMV-directed treatments may alter the cellular immune response within the allograft.
全球多达90%的人口感染过巨细胞病毒（CMV），这是一种疱疹病毒，在宿主一生中处于潜伏状态，并导致免疫失调。CMV是实体器官移植后预后不良的关键危险因素，尽管肺移植受者（LTR）感染CMV的风险最高，且与其他实体器官移植受者相比，CMV相关的合并症更多。尽管有强效抗病毒药物，但CMV仍然是慢性肺移植功能障碍（CLAD）、再次移植和死亡的重要驱动因素。此外，CMV抗病毒预防的广泛应用并非没有不良反应，常常需要停药。因此，迫切需要了解肺移植后对CMV的免疫反应。本综述确定了CMV免疫反应各方面的关键要素，并强调了对肺移植耐受和损伤的影响。特别关注了在CMV感染和再激活期间在肺中起重要作用的适应性和先天性免疫细胞的细胞亚群。深入综述了异源免疫反应的概念，包括它们如何形成以及如何驱动组织和移植特异性免疫。本综述的其他重要目标是详细阐述NK细胞在CMV相关结局中的新作用，此外还讨论了既往肺部疾病引起的CMV免疫功能紊乱。最后，本综述确定了CMV定向治疗可能改变移植肺内细胞免疫反应的潜在机制。
