Chronic viral infections lead to CD8(+) T cell exhaustion, characterized by impaired cytokine secretion. The presence of the immune-regulatory cytokine IL-10 promotes chronic lymphocytic choriomeningitis virus (LCMV) Clone 13 infection in mice, whereas the absence of IL-10/IL-10R signaling early during infection results in viral clearance and higher percentages and numbers of antiviral, cytokine-producing T cells. However, it is currently unclear which cell populations and effector molecules are crucial to protect against chronic infection. In this study, we demonstrate that antiviral, LCMV-binding, non-neutralizing antibodies are needed, in addition to CD4(+) and CD8(+) T cells, to clear a high-dose LCMV infection in mice, in the absence of IL-10. The interaction between CD4(+) T cells and B cells in B-cell follicles via CD40/CD40L, in addition to class switch and/or somatic hypermutation, is crucial for viral control in the absence of IL-10. Interestingly, transfer of LCMV-binding non-neutralizing antibodies protected recipients from chronic infection. In addition, viral clearance in the absence of IL-10R signaling was independent of activating Fcγ receptors and complement. These data highlight that non-neutralizing antibodies effectively contribute to the control of LCMV infection when present prior to infection, suggesting that the induction of neutralizing antibodies is not implicitly necessary for the generation of successful vaccines.

中文翻译：

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非中和抗体可独立于激活FcγR或补体而保护免受慢性LCMV感染。

慢性病毒感染导致CD8（+）T细胞衰竭，其特征在于细胞因子分泌受损。免疫调节性细胞因子IL-10的存在可促进小鼠慢性淋巴细胞性脉络膜脑膜炎病毒（LCMV）Clone 13感染，而在感染过程中早期缺乏IL-10 / IL-10R信号传导会导致病毒清除率和更高的百分比和数量。抗病毒，产生细胞因子的T细胞。然而，目前尚不清楚哪些细胞群和效应分子对于预防慢性感染至关重要。在这项研究中，我们证明除了CD4（+）和CD8（+）T细胞外，还需要抗病毒，LCMV结合，非中和抗体来清除小鼠中的大剂量LCMV感染， IL-10。通过CD40 / CD40L，B细胞滤泡中CD4（+）T细胞和B细胞之间的相互作用，除类别转换和/或体细胞超突变外，对于缺乏IL-10的病毒控制至关重要。有趣的是，结合LCMV的非中和抗体的转移可保护受体免受慢性感染。此外，在没有IL-10R信号传导的情况下，病毒清除率与激活Fcγ受体和补体无关。这些数据突出表明，非中和抗体在感染前存在时有效地有助于控制LCMV感染，这表明中和抗体的诱导对于成功疫苗的产生并不是隐含的。在没有IL-10R信号传导的情况下，病毒清除率与激活Fcγ受体和补体无关。这些数据突出表明，非中和抗体在感染前存在时有效地有助于控制LCMV感染，这表明中和抗体的诱导对于成功疫苗的产生并不是隐含的。在没有IL-10R信号传导的情况下，病毒清除率与激活Fcγ受体和补体无关。这些数据突出表明，非中和抗体在感染前存在时有效地有助于控制LCMV感染，这表明中和抗体的诱导对于成功疫苗的产生并不是隐含的。