In retroviral infections, different immunological mechanisms are involved in the development of a chronic infection. In the Friend virus (FV) model, regulatory T cells (Tregs) were found to induce CD8⁺ T cell dysfunction before viral clearance is achieved and thus contribute to viral chronicity. Although studied for decades, the exact suppressive mechanisms of Tregs in the FV model remain elusive and an unavailable therapeutic target. However, extracellular IL-2 and intracellular NF-κB signaling were shown to be important pathways for Treg expansion and activation. Therefore, we decided to focus on these two pathways to test therapeutic approaches inhibiting Treg activation during FV infection. In this study, we show that the inhibition of either IL-2 or the NF-κB subunit c-Rel, impaired Treg expansion and activation at 2 weeks post-FV infection. Total numbers of Tregs as well as activated Tregs were reduced in FV-infected mice after treatment with anti-IL-2 antibodies or the c-Rel blocking reagent pentoxifylline. Surprisingly, this did not affect the expansion or function of virus-specific CD8⁺ T cells nor viral loads in the spleen. However, our data suggest that neutralization of IL-2 as well as blocking c-Rel efficiently inhibits virus-induced Treg expansion.

中文翻译：

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IL-2或NF-κB亚基c-Rel依赖信号的抑制抑制了急性朋友逆转录病毒感染过程中调节性T细胞的扩增。

在逆转录病毒感染中，慢性感染的发展涉及不同的免疫学机制。在Friend病毒（FV）模型中，发现调节性T细胞（Tregs）在实现病毒清除之前可诱导CD8 ⁺ T细胞功能障碍，从而有助于病毒慢性发作。尽管已研究了数十年，但FV模型中Treg的确切抑制机制仍然难以捉摸，并且是无法获得的治疗靶标。然而，胞外IL-2和细胞内NF- κ乙信令被证明是对调节性T细胞扩增和活化重要途径。因此，我们决定专注于这两个途径来测试抑制FV感染期间Treg激活的治疗方法。在这项研究中，我们表明，无论是IL-2或NF-所述的抑制κB亚基c-Rel，在FV感染后2周时Treg扩增和活化受损。用抗IL-2抗体或c-Rel阻断剂己酮可可碱治疗后，感染FV的小鼠的Treg和活化Treg总数减少。出人意料的是，这既不影响病毒特异性CD8 ⁺ T细胞的扩增或功能，也不影响脾脏中的病毒载量。但是，我们的数据表明，IL-2的中和作用以及阻断c-Rel均可有效抑制病毒诱导的Treg扩增。