Yagyu K, Steinhoff G, Duijvestijn A M, Bruggeman C A, Matsumoto H, van Breda Vriesman P J
Department of Thoracic Surgery, University of Tokyo, Japan.
J Heart Lung Transplant. 1992 Nov-Dec;11(6):1031-40.
Reactivation of latent rat cytomegalovirus (RCMV) from a lung allograft or from a recipient was studied in RCMV-mismatched combinations (donor [D]-/recipient [R]+, D+/R-, and D+/R+) with latently infected lung grafts and chronically infected rats in an inbred rat model. Nineteen transplants in a major histocompatibility complex different strain combination (Brown-Norway/Lewis) were immunosuppressed daily (cyclosporine, azathioprine, and prednisolone) from day 3 after orthotopic left lung transplantation and killed on days 3, 6, and 21. Control groups consisted of nine chronically RCMV-infected rats with immunosuppression without transplantation and six allografts with immunosuppression without RCMV infection. Reactivation of latent RCMV was tested by immunohistochemical staining with monoclonal antibodies against RCMV-induced antigens and by plaque assays of the virus in the salivary glands. The following results were obtained: (1) All allotransplants developed acute ongoing rejection on days 3 and 6, and the rejection was resolved on day 21 by immunosuppression. (2) Reactivation was observed in allotransplanted groups, but not in the control rats. (3) In the D+/R+ and D-/R+ groups on days 3 and 6, the number of RCMV-related antigen-positive cells increased in the recipient spleen and lymph nodes and in the bronchus-associated lymphoid tissue of the donor lung in the D-/R+ group, but not in the chronically RCMV-infected controls. (4) In the D+/R- group on day 6, RCMV-induced antigen-positive cells were observed in the spleen and lymph nodes of the recipient and also around the vessels in the recipient lung. (5) In the D-/R+ group, vascular endothelial cells or mildly infiltrated mononuclear cell subpopulations around the vessels in the lung allograft showed weakly positive staining against RCMV-related antigens on day 6. (6) After the initial acute rejection on days 3 and 6 was treated by immunosuppressive drugs, reactivated acute RCMV infection became chronic or latent again on day 21. We conclude that RCMV infection could be transferred with latently infected lung allografts by reactivation of latent RCMV. In rats, as in man, alloimmune responses seemed to have a definite influence on the reactivation of latent RCMV after lung transplantation.
在一个近交系大鼠模型中，我们研究了在大鼠巨细胞病毒（RCMV）不匹配的组合（供体[D]-/受体[R]+、D+/R-和D+/R+）中，来自肺移植或受体的潜伏性RCMV再激活情况，这些组合中有潜伏感染的肺移植和慢性感染的大鼠。在原位左肺移植后第3天开始，对19例主要组织相容性复合体不同品系组合（布朗-挪威/刘易斯）的移植大鼠每日进行免疫抑制（环孢素、硫唑嘌呤和泼尼松龙），并在第3、6和21天处死。对照组包括9只慢性RCMV感染且接受免疫抑制但未进行移植的大鼠，以及6只接受免疫抑制但未感染RCMV的同种异体移植大鼠。通过用抗RCMV诱导抗原的单克隆抗体进行免疫组织化学染色以及对唾液腺中的病毒进行空斑试验来检测潜伏性RCMV的再激活。获得了以下结果：（1）所有同种异体移植在第3天和第6天均出现急性进行性排斥反应，通过免疫抑制在第21天排斥反应得到缓解。（2）在同种异体移植组中观察到再激活，但在对照大鼠中未观察到。（3）在第3天和第6天的D+/R+和D-/R+组中，受体脾脏和淋巴结以及D-/R+组供体肺的支气管相关淋巴组织中RCMV相关抗原阳性细胞数量增加，但在慢性RCMV感染的对照组中未增加。（4）在第6天的D+/R-组中，在受体的脾脏和淋巴结以及受体肺血管周围观察到RCMV诱导的抗原阳性细胞。（5）在D-/R+组中，肺移植同种异体血管周围的血管内皮细胞或轻度浸润的单核细胞亚群在第6天对RCMV相关抗原呈弱阳性染色。（6）在第3天和第6天的初始急性排斥反应经免疫抑制药物治疗后，再激活的急性RCMV感染在第21天再次变为慢性或潜伏性。我们得出结论，RCMV感染可通过潜伏性RCMV的再激活与潜伏感染的肺同种异体移植一起转移。在大鼠中，如同在人类中一样，同种免疫反应似乎对肺移植后潜伏性RCMV的再激活有明确影响。
