Klenovsek Karin, Weisel Florian, Schneider Andrea, Appelt Uwe, Jonjic Stipan, Messerle Martin, Bradel-Tretheway Birgit, Winkler Thomas H, Mach Michael
Institute for Clinical and Molecular Virology, University Hospital Erlangen, Schlossgarten 4, 91054 Erlangen, Germany.
Blood. 2007 Nov 1;110(9):3472-9. doi: 10.1182/blood-2007-06-095414. Epub 2007 Jul 26.
Severe disease associated with cytomegalovirus (CMV) infection is still a major problem in patients who undergo transplantation. Support of the patients' immune defense against the virus is a major goal in transplantation medicine. We have used the murine model of CMV (MCMV) to investigate the potential of a cell-based strategy to support the humoral antiviral immune response. Immunocompetent C57BL/6 mice were infected with MCMV, and memory B cells from the immune animals were adoptively transferred into T-cell- and B-cell-deficient RAG-1(-/-) mice. Following MCMV infection, a virus-specific IgG response developed within 4 to 7 days in the recipient animals. Concomitantly, a significant reduction in viral titers and DNA copies in several organs was observed. In addition, the memory B-cell transfer provided long-term protection from the lethal course of the infection that is invariably seen in immunodeficient animals. Transfer of memory B cells was also effective in protecting from an already ongoing viral infection, indicating a therapeutic potential of virus-specific memory B cells. T cells were not involved in this process. Our data provide evidence that a cell-based strategy to support the humoral immune response can be effective to combat infectious pathogens in severely immunodeficient hosts.
巨细胞病毒(CMV)感染相关的严重疾病仍是移植患者面临的主要问题。支持患者针对该病毒的免疫防御是移植医学的主要目标。我们利用巨细胞病毒小鼠模型(MCMV)来研究基于细胞的策略支持体液抗病毒免疫反应的潜力。将免疫活性C57BL/6小鼠感染MCMV,然后将来自免疫小鼠的记忆B细胞过继转移到T细胞和B细胞缺陷的RAG-1(-/-)小鼠体内。感染MCMV后,受体动物在4至7天内产生了病毒特异性IgG反应。同时,观察到多个器官中的病毒滴度和DNA拷贝数显著降低。此外,记忆B细胞转移为免疫缺陷动物中常见的致死性感染病程提供了长期保护。记忆B细胞转移在保护免受已发生的病毒感染方面也有效,表明病毒特异性记忆B细胞具有治疗潜力。T细胞未参与此过程。我们的数据证明,支持体液免疫反应的基于细胞的策略在对抗严重免疫缺陷宿主中的感染性病原体方面可能有效。