Human cytomegalovirus (HCMV) persistently infects 40% to 100% of the human population worldwide. Experimental and clinical evidence indicates that humoral immunity to HCMV plays an important role in restricting virus dissemination and protecting the infected host from disease. Specific immunoglobulin preparations from pooled plasma of adults selected for high titers of HCMV antibodies have been used for the prevention of CMV disease in transplant recipients and pregnant women. Even though incubation of HCMV particles with these preparations leads to the neutralization of viral infectivity, it is still unclear whether the antibody-treated HCMV particles (referred to here as HCMV-Ab) enter the cells and modulate antiviral immune responses. Here we demonstrate that HCMV-Ab did enter macrophages. HCMV-Ab did not initiate the expression of immediate early antigens (IEAs) in macrophages, but they induced an antiviral state and rendered the cells less susceptible to HCMV infection upon challenge. Resistance to HCMV infection seemed to be due to the activation of intrinsic restriction factors and was independent of interferons. In contrast to actively infected cells, autologous NK cells did not degranulate against HCMV-Ab-treated macrophages, suggesting that these cells may not be eliminated by innate effector cells. Interestingly, HCMV-Ab-treated macrophages stimulated the proliferation of autologous adaptive CD4⁺ and CD8⁺ T cells. Our findings not only expand the current knowledge on virus-antibody immunity but may also be relevant for future vaccination strategies.

IMPORTANCE Human cytomegalovirus (HCMV), a common herpesvirus, establishes benign but persistent infections in immunocompetent hosts. However, in subjects with an immature or dysfunctional immune system, HCMV is a major cause of morbidity and mortality. Passive immunization has been used in different clinical settings with variable clinical results. Intravenous hyperimmune globulin preparations (IVIg) are obtained from pooled adult human plasma selected for high anti-CMV antibody titers. While HCMV neutralization can be shown in vitro using different systems, data are lacking regarding the cross-influence of IVIg administration on the cellular immune responses. The aim of this study was to evaluate the effects of IVIg on distinct components of the immune response against HCMV, including antigen presentation by macrophages, degranulation of innate natural killer cells, and proliferation of adaptive CD4⁺ and CD8⁺ T cells.

人类巨细胞病毒（HCMV）持续感染全世界40％至100％的人口。实验和临床证据表明，对HCMV的体液免疫在限制病毒传播和保护感染宿主免受疾病的侵害中起着重要作用。来自成人合并血浆的特定免疫球蛋白制剂已被选择用于高滴度HCMV抗体，已用于预防移植受者和孕妇的CMV疾病。即使将HCMV颗粒与这些制剂一起温育导致病毒感染力的中和，但仍不清楚抗体处理的HCMV颗粒（在此称为HCMV-Ab）是否进入细胞并调节抗病毒免疫应答。在这里，我们证明HCMV-Ab确实进入了巨噬细胞。HCMV-Ab不会在巨噬细胞中启动立即早期抗原（IEA）的表达，但它们诱导了抗病毒状态，使细胞在受到攻击后不易受到HCMV感染。对HCMV感染的抗药性似乎是由于内在限制因子的激活所致，并且与干扰素无关。与主动感染的细胞相反，自体NK细胞未针对HCMV-Ab处理的巨噬细胞脱颗粒，这表明这些细胞可能不会被先天性效应细胞所消除。有趣的是，HCMV-Ab处理的巨噬细胞刺激了自体适应性CD4的增殖 对HCMV感染的抗药性似乎是由于内在限制因子的激活所致，并且与干扰素无关。与主动感染的细胞相反，自体NK细胞未针对HCMV-Ab处理的巨噬细胞脱颗粒，这表明这些细胞可能不会被先天性效应细胞所消除。有趣的是，HCMV-Ab处理的巨噬细胞刺激了自体适应性CD4的增殖 对HCMV感染的抗药性似乎是由于内在限制因子的激活所致，并且与干扰素无关。与主动感染的细胞相反，自体NK细胞未针对HCMV-Ab处理的巨噬细胞脱颗粒，这表明这些细胞可能不会被先天性效应细胞所消除。有趣的是，HCMV-Ab处理的巨噬细胞刺激了自体适应性CD4的增殖⁺和CD8 ⁺ T细胞。我们的发现不仅扩展了当前对病毒抗体免疫的知识，而且可能与未来的疫苗接种策略有关。

重要信息人类巨细胞病毒（HCMV）是一种常见的疱疹病毒，可在具有免疫能力的宿主中建立良性但持续的感染。然而，在免疫系统未成熟或功能异常的受试者中，HCMV是发病率和死亡率的主要原因。被动免疫已在不同的临床环境中使用，并产生了不同的临床结果。静脉超免疫球蛋白制剂（IVIg）从为高抗CMV抗体滴度选择的合并成人血浆中获得。HCMV中和可以在体外显示使用不同的系统，缺乏有关IVIg给药对细胞免疫反应的交叉影响的数据。这项研究的目的是评估IVIg对HCMV免疫反应的不同组成部分的影响，包括巨噬细胞呈递抗原，先天性自然杀伤细胞脱颗粒以及适应性CD4 ⁺和CD8 ⁺ T细胞的增殖。