持续性病毒感染期间Fcγ受体介导的抗体效应功能的抑制
Suppression of Fcγ-receptor-mediated antibody effector function during persistent viral infection.
作者信息
Yamada Douglas H, Elsaesser Heidi, Lux Anja, Timmerman John M, Morrison Sherie L, de la Torre Juan Carlos, Nimmerjahn Falk, Brooks David G
机构信息
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Institute of Genetics, Department of Biology, University of Erlangen-Nürnberg, Erwin-Rommelstrasse 3, 91058, Erlangen, Germany.
出版信息
Immunity. 2015 Feb 17;42(2):379-390. doi: 10.1016/j.immuni.2015.01.005. Epub 2015 Feb 10.
Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.
了解病毒如何破坏宿主免疫力并持续存在对于制定消除感染的策略至关重要。慢性病毒感染期间的T细胞耗竭已得到充分描述，但对抗体介导的效应活性的影响尚不清楚。在此，我们表明，持续感染淋巴细胞性脉络丛脑膜炎病毒（LCMV）的小鼠中产生的免疫复合物数量增加会抑制多种Fcγ受体（FcγR）功能。大量的免疫复合物抑制了抗体介导的细胞清除、治疗性抗体对LCMV感染细胞和表达人CD20的肿瘤的杀伤作用，以及减少了免疫复合物介导的向T细胞的交叉呈递。FcγR活性的抑制不是由于抑制性FcγR或高浓度的游离抗体，并且当持续感染的小鼠特异性缺乏免疫复合物时，FcγR的正常功能得以恢复。因此，我们确定了病毒持续存在期间的一种免疫抑制机制，这对于理解旨在控制病原体的有效抗体活性具有重要意义。
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