Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany; Faculty of Biology, University of Freiburg, Freiburg, Germany.
Eur J Immunol. 2013 Sep;43(9):2338-48. doi: 10.1002/eji.201343565. Epub 2013 Jul 15.
CD8(+) T cells have an essential role in controlling lymphocytic choriomeningitis virus (LCMV) infection in mice. Here, we examined the contribution of humoral immunity, including nonneutralizing antibodies (Abs), in this infection induced by low virus inoculation doses. Mice with impaired humoral immunity readily terminated infection with the slowly replicating LCMV strain Armstrong but showed delayed virus elimination after inoculation with the faster replicating LCMV strain WE and failed to clear the rapidly replicating LCMV strain Docile, which is in contrast to the results obtained with wild-type mice. Thus, the requirement for adaptive humoral immunity to control the infection was dependent on the replication speed of the LCMV strains used. Ab transfers further showed that LCMV-specific IgG Abs isolated from LCMV immune serum accelerated virus elimination. These Abs were mainly directed against the viral nucleoprotein (NP) and completely lacked virus neutralizing activity. Moreover, mAbs specific for the LCMV NP were also able to decrease viral titers after transfer into infected hosts. Intriguingly, neither C3 nor Fcγ receptors were required for the antiviral activity of the transferred Abs. In conclusion, our study suggests that rapidly generated nonneutralizing Abs specific for the viral NP speed up virus elimination and thereby may counteract T-cell exhaustion.
CD8(+) T 细胞在控制小鼠淋巴细胞性脉络丛脑膜炎病毒 (LCMV) 感染中起着至关重要的作用。在这里，我们研究了体液免疫（包括非中和抗体）在低病毒接种剂量诱导的这种感染中的作用。体液免疫受损的小鼠容易终止缓慢复制的 LCMV 株 Armstrong 的感染，但在接种快速复制的 LCMV 株 WE 后，病毒清除延迟，无法清除快速复制的 LCMV 株 Docile，这与野生型小鼠的结果形成对比。因此，控制感染需要适应性体液免疫，这取决于所使用的 LCMV 株的复制速度。Ab 转移进一步表明，从 LCMV 免疫血清中分离的 LCMV 特异性 IgG Ab 加速了病毒清除。这些 Ab 主要针对病毒核蛋白（NP），完全缺乏病毒中和活性。此外，针对 LCMV NP 的 mAb 也能够在转移到感染宿主后降低病毒滴度。有趣的是，转移的 Ab 发挥抗病毒作用既不需要 C3 也不需要 Fcγ 受体。总之，我们的研究表明，针对病毒 NP 的快速产生的非中和 Ab 加速了病毒清除，从而可能对抗 T 细胞耗竭。
