Comoli Patrizia, Labirio Massimo, Basso Sabrina, Baldanti Fausto, Grossi Paolo, Furione Milena, Viganò Mario, Fiocchi Roberto, Rossi Giorgio, Ginevri Fabrizio, Gridelli Bruno, Moretta Antonia, Montagna Daniela, Locatelli Franco, Gerna Giuseppe, Maccario Rita
Department of Pediatrics, Immunology Laboratory, IRCCS Policlinico S. Matteo, P.le Golgi 2, 27100 Pavia, Italy.
Blood. 2002 Apr 1;99(7):2592-8. doi: 10.1182/blood.v99.7.2592.
Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorders (PTLDs) are a well-recognized complication of immunosuppression in solid organ transplant recipients. The reported therapeutic approaches are frequently complicated by rejection, toxicity, and other infectious pathologies, and overall mortality in patients with unresponsive PTLD remains high. Thus, low-toxicity treatment options or, preferably, some form of prophylactic/preemptive intervention are warranted to improve PTLD outcome in this setting. We assessed whether transfer of EBV-specific cytotoxic T lymphocytes (CTLs) generated in vitro from the peripheral blood of allograft recipients receiving immunosuppression could increase EBV-specific killing in vivo without augmenting the probability of graft rejection. Autologous EBV-specific CTLs were generated for 23 patients who were identified as being at risk of developing PTLD through the finding of elevated EBV DNA load. Of the 23 patients, 7 received 1 to 5 infusions of EBV-specific CTLs. CTL transfer was well tolerated, and none of the patients showed any evidence of rejection. An increase of the EBV-specific cytotoxicity was observed after infusion, notwithstanding continuation of immunosuppressive therapy. EBV DNA levels had a 1.5- to 3-log decrease in 5 patients, whereas in the other 2 graft recipients CTL transfer had no apparent stable effect on EBV load. Our data suggest that the infusion of autologous EBV-specific CTLs obtained from peripheral blood mononuclear cells recovered at the time of viral reactivation is able to augment virus-specific immune response and to reduce viral load in organ transplant recipients. This approach may, therefore, be safely used as prophylaxis of EBV-related lymphoproliferative disorders in these patients, following a strategy of preemptive therapy guided by EBV DNA levels.
爱泼斯坦-巴尔病毒（EBV）相关的移植后淋巴细胞增生性疾病（PTLD）是实体器官移植受者免疫抑制公认的并发症。报道的治疗方法常常因排斥反应、毒性和其他感染性病变而变得复杂，对治疗无反应的PTLD患者的总体死亡率仍然很高。因此，需要低毒性的治疗选择，或者更理想的是某种形式的预防性/先发制性干预，以改善这种情况下PTLD的治疗结果。我们评估了从接受免疫抑制的同种异体移植受者外周血体外产生的EBV特异性细胞毒性T淋巴细胞（CTL）的转移是否能在不增加移植排斥概率的情况下增强体内EBV特异性杀伤作用。通过发现EBV DNA载量升高，为23名被确定有发生PTLD风险的患者产生了自体EBV特异性CTL。在这23名患者中，7名接受了1至5次EBV特异性CTL输注。CTL转移耐受性良好，没有患者出现任何排斥反应的迹象。尽管继续进行免疫抑制治疗，但输注后观察到EBV特异性细胞毒性增加。5名患者的EBV DNA水平下降了1.5至3个对数，而在其他2名移植受者中，CTL转移对EBV载量没有明显的稳定作用。我们的数据表明，输注在病毒重新激活时回收的外周血单个核细胞获得的自体EBV特异性CTL能够增强病毒特异性免疫反应并降低器官移植受者的病毒载量。因此，按照由EBV DNA水平指导的先发制性治疗策略，这种方法可以安全地用作这些患者EBV相关淋巴细胞增生性疾病的预防措施。
