Kuo Elbert, Bharat Ankit, Goers Trudie, Chapman Will, Yan Le, Street Tyler, Lu Wei, Walter Michael, Patterson Alexander, Mohanakumar Thalachallour
Department of Surgery, Washington University, St. Louis, Missouri 63110, USA.
Ann Thorac Surg. 2006 Sep;82(3):1043-50. doi: 10.1016/j.athoracsur.2006.03.120.
The long-term survival after human lung transplantation is limited by bronchiolitis obliterans syndrome (BOS). Clinically, community-acquired respiratory viral infections have been correlated with an increased incidence of BOS. The goal of this study was to investigate the role of respiratory viral infections in chronic lung allograft rejection using the murine orthotopic tracheal transplantation model.
Eighty orthotopic tracheal transplants were performed using BALB/c and C57BL/6 mice. Recipient mice were infected intranasally with Sendai virus (SdV), a murine parainfluenza type I virus. Experiments altering the infectious dose, infection time, harvest time, allogeneic response, and viral response were performed. Tracheal allograft rejection was monitored using percent fibrosis and lamina propria to cartilage ratio measurements. Interferon-gamma ELISPOT analysis against irradiated donor (BALB/c) splenocytes was used as immunologic indicator of alloreactivity after transplantation.
Sendai virus infection revealed a dose-dependent transient suppression of alloreactivity with a decrease in tracheal allograft fibrosis and frequency of alloreactive T cells at 30 days. This immunosuppression was reversed by day 60, leading to increased tracheal allograft fibrosis with a concomitant increase in the frequency of interferon-gamma producing alloreactive T cells. Pretransplant sensitization with donor antigens prevented the initial suppression of alloreactivity due to SdV infection. Furthermore, pretransplant immunization against SdV infection resulted in rapid clearing of the infection and reduced the immunopathology of rejection.
Respiratory viral infections can cause enhanced tracheal allograft rejection despite the initial phase of transient immunosuppression. Early treatment or vaccination against the respiratory infections may represent a viable intervention to reduce the risk of chronic rejection.
细支气管闭塞综合征（BOS）限制了人类肺移植后的长期生存。临床上，社区获得性呼吸道病毒感染与BOS发病率增加相关。本研究的目的是使用小鼠原位气管移植模型研究呼吸道病毒感染在慢性肺移植排斥反应中的作用。
使用BALB/c和C57BL/6小鼠进行80例原位气管移植。受体小鼠经鼻感染仙台病毒（SdV），一种鼠I型副流感病毒。进行了改变感染剂量、感染时间、收获时间、同种异体反应和病毒反应的实验。使用纤维化百分比和固有层与软骨比例测量来监测气管同种异体移植排斥反应。针对照射后的供体（BALB/c）脾细胞的干扰素-γ ELISPOT分析用作移植后同种异体反应性的免疫指标。
仙台病毒感染显示出剂量依赖性的同种异体反应性短暂抑制，在30天时气管同种异体移植纤维化减少，同种异体反应性T细胞频率降低。这种免疫抑制在第60天时逆转，导致气管同种异体移植纤维化增加，同时产生干扰素-γ的同种异体反应性T细胞频率增加。用供体抗原进行移植前致敏可防止由于SdV感染引起的同种异体反应性的初始抑制。此外，移植前针对SdV感染的免疫接种导致感染快速清除，并减少了排斥反应的免疫病理学。
尽管有短暂免疫抑制的初始阶段，但呼吸道病毒感染可导致气管同种异体移植排斥反应增强。针对呼吸道感染的早期治疗或疫苗接种可能是降低慢性排斥反应风险的可行干预措施。
