Nehete Pramod N, Nehete Bharti P, Chitta Sriram
Department of Comparative Medicine, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, USA.
The University of Texas Graduate School of Biomedical Sciences, Houston, Texas, USA.
Viral Immunol. 2025 Jan-Feb;38(1):12-22. doi: 10.1089/vim.2024.0080. Epub 2025 Jan 2.
The increasing use of immune suppressive monoclonal antibodies in the treatment of organ transplant recipients and patients with oncologic, neurological, and autoimmune diseases can lead to serious morbidity and mortality from the reactivation of viral agents that persist in humans. The squirrel monkey polyomaviruses are naturally found in Bolivian squirrel monkeys (SQM) and may be a useful model for the study of polyomavirus-associated pathogenesis and experimental treatment and prevention strategies. Two diverse groups of squirrel monkeys were given, a single dose of an anti-B cell antibody (rituximab) resulting in complete depletion of B cells (CD20+), while an anti-CD8 monoclonal antibody (7 pt-3F9) resulted in a transient depletion of CD8+ lymphocytes compared with control animals (group with no infusion with either of the monoclonal antibodies). The animals remained clinically healthy, with no pathological symptoms suggesting that the intensity and/or duration of immune suppression were inadequate to trigger pathogenic reactivation of the latent polyoma and herpes viruses. We observed a transient reduction in circulating plasma cytokines, IL-2, IFN-γ, and IL-12 reduced JC and BK viral protein-specific proliferative responses in both the CD8 and CD20 depletion groups. This study clearly elucidates the consequences of the use of depletion monoclonal antibodies in immune suppression modalities in the treatment of human malignancies and during transplantation, and SQM acts as a good model in the selection of dosage at which activation of latent viruses is at a minimum, with no pathological consequences.
在器官移植受者以及患有肿瘤、神经和自身免疫性疾病的患者治疗中，免疫抑制性单克隆抗体的使用日益增加，这可能导致潜伏在人体内的病毒重新激活，从而引发严重的发病和死亡。松鼠猴多瘤病毒天然存在于玻利维亚松鼠猴（SQM）体内，可能是研究多瘤病毒相关发病机制以及实验性治疗和预防策略的有用模型。给两组不同的松鼠猴分别单次注射一种抗B细胞抗体（利妥昔单抗），导致B细胞（CD20+）完全耗竭，而抗CD8单克隆抗体（7 pt-3F9）导致CD8+淋巴细胞短暂耗竭，与之相比，对照动物（未注射任何一种单克隆抗体的组）则没有这种情况。这些动物在临床上保持健康，没有病理症状，这表明免疫抑制的强度和/或持续时间不足以触发潜伏的多瘤病毒和疱疹病毒的致病性重新激活。我们观察到循环血浆细胞因子IL-2、IFN-γ和IL-12短暂减少，在CD8和CD20耗竭组中，JC和BK病毒蛋白特异性增殖反应均降低。这项研究清楚地阐明了在治疗人类恶性肿瘤和移植过程中，使用耗竭性单克隆抗体进行免疫抑制模式的后果，并且松鼠猴在选择使潜伏病毒激活降至最低且无病理后果的剂量方面是一个很好的模型。
