Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection

被引：54
|
作者：
Yamada, Douglas H. [1 ]
Elsaesser, Heidi [1 ]
Lux, Anja [6 ]
Timmerman, John M. [3 ,4 ]
Morrison, Sherie L. [1 ]
de la Torre, Juan Carlos [5 ]
Nimmerjahn, Falk [6 ]
Brooks, David G. [1 ,2 ]
机构：
[1] Univ Calif Los Angeles, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, UCLA AIDS Inst, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[5] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA
[6] Univ Erlangen Nurnberg, Inst Genet, Dept Biol, D-91058 Erlangen, Germany
来源：
IMMUNITY | 2015年 / 42卷 / 02期
基金：
美国国家卫生研究院;
关键词：
BROADLY NEUTRALIZING ANTIBODIES; DENDRITIC CELLS; HIV-INFECTION; T-CELLS; B-CELLS; VIRUS; THERAPY; IGG; EFFICACY; IMMUNITY;
D O I：
10.1016/j.immuni.2015.01.005
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
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 anti-body- 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 Fc gamma-receptor (Fc gamma R) 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 Fc gamma R activity was not due to inhibitory Fc gamma Rs or high concentrations of free antibody, and proper Fc gamma R 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.
引用
收藏
页码：379 / 390
页数：12
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