Preemptive CD8 T-Cell Immunotherapy of Acute Cytomegalovirus Infection Prevents Lethal Disease, Limits the Burden of Latent Viral Genomes, and Reduces the Risk of Virus Recurrence
Preemptive CD8 T-Cell Immunotherapy of Acute Cytomegalovirus Infection Prevents Lethal Disease, Limits the Burden of Latent Viral Genomes, and Reduces the Risk of Virus Recurrence
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急性巨细胞病毒感染的先发性 CD8 T 细胞免疫疗法可预防致命性疾病，限制潜伏病毒基因组的负担，并降低病毒复发的风险
DOI：
10.1128/jvi.72.3.1797-1804.1998
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发表时间：
1998
影响因子：
5.4
通讯作者：
M. Reddehase
中科院分区：
文献类型：
--
作者：
H. Steffens;Sabine K. Kurz;R. Holtappels;M. Reddehase
摘要 在免疫功能正常的宿主中，原发性巨细胞病毒 (CMV) 感染可通过免疫反应消除，而不会引起明显的疾病。然而，病毒基因组并未被清除，而是保持在潜伏状态，这会带来病毒复发和随之而来的器官疾病的风险。通过使用鼠 CMV 作为模型，我们之前已经表明，多个器官隐藏着潜在的 CMV，并且重新激活的发生率由各个器官中的病毒 DNA 载量决定（M. J. Reddehase、M. Balthesen、M. Rapp、S. Jonjic、I. Pavic 和 U. H. Koszinowski. J. Exp. Med. 179:185–193, 1994）。这预示着能够限制潜伏病毒基因组负载的治疗干预也应该降低病毒复发的风险。在这里，我们展示了针对免疫功能低下的骨髓移植受者的 CMV 感染的先发性 CD8 T 细胞免疫疗法的益处和局限性。抗病毒 CD8 T 细胞可预防 CMV 疾病并加速生产性感染的消退。该疗法还降低了器官中潜在 CMV DNA 的负载，从而降低了复发率。因此，这些数据为利用 CD8 T 细胞对人类 CMV 疾病进行先发性细胞免疫治疗的临床试验提供了进一步的支持论据。然而，CD8 T 细胞未能清除病毒 DNA。 DNA 负载的治疗敏感部分因器官而异，且在肺部最高。不变的、抗治疗负荷的存在表明免疫系统逃避机制在巨细胞病毒潜伏期的建立中发挥着作用。
ABSTRACT In the immunocompetent host, primary cytomegalovirus (CMV) infection is resolved by the immune response without causing overt disease. The viral genome, however, is not cleared but is maintained in a latent state that entails a risk of virus recurrence and consequent organ disease. By using murine CMV as a model, we have shown previously that multiple organs harbor latent CMV and that reactivation occurs with an incidence that is determined by the viral DNA load in the respective organ (M. J. Reddehase, M. Balthesen, M. Rapp, S. Jonjic, I. Pavic, and U. H. Koszinowski. J. Exp. Med. 179:185–193, 1994). This predicts that a therapeutic intervention capable of limiting the load of latent viral genome should also reduce the risk of virus recurrence. Here we demonstrate the benefits and the limits of a preemptive CD8 T-cell immunotherapy of CMV infection in the immunocompromised bone marrow transplantation recipient. Antiviral CD8 T cells prevented CMV disease and accelerated the resolution of productive infection. The therapy also resulted in a lower load of latent CMV DNA in organs and consequently reduced the incidence of recurrence. The data thus provide a further supporting argument for clinical trials of preemptive cytoimmunotherapy of human CMV disease with CD8 T cells. However, CD8 T cells failed to clear the viral DNA. The therapy-susceptible portion of the DNA load differed between organs and was highest in the lungs. The existence of an invariant, therapy-resistant load suggests a role for immune system evasion mechanisms in the establishment of CMV latency.
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人类病毒性疾病过继性 T 细胞治疗原则。
影响因子：
29.7
作者：
Riddell,SR;Greenberg,PD
通讯作者：
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DOI：
10.1093/clinids/12.supplement_7.s776
发表时间：
1990
期刊：
Reviews of infectious diseases
影响因子：
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作者：
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影响因子：
20.3
作者：
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通讯作者：
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影响因子：
158.5
作者：
QUINNAN, GV;KIRMANI, N;BURNS, WH
通讯作者：
BURNS, WH