Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92037, USA.
J Immunol. 2012 Sep 1;189(5):2432-40. doi: 10.4049/jimmunol.1200799. Epub 2012 Jul 23.
The precise immune components required for protection against a respiratory Orthopoxvirus infection, such as human smallpox or monkeypox, remain to be fully identified. In this study, we used the virulent Western Reserve strain of vaccinia virus (VACV-WR) to model a primary respiratory Orthopoxvirus infection. Naive mice infected with VACV-WR mounted an early CD8 T cell response directed against dominant and subdominant VACV-WR Ags, followed by a CD4 T cell and Ig response. In contrast to other VACV-WR infection models that highlight the critical requirement for CD4 T cells and Ig, we found that only mice deficient in CD8 T cells presented with severe cachexia, pulmonary inflammation, viral dissemination, and 100% mortality. Depletion of CD8 T cells at specified times throughout infection highlighted that they perform their critical function between days 4 and 6 postinfection and that their protective requirement is critically dictated by initial viral load and virulence. Finally, the ability of adoptively transferred naive CD8 T cells to protect RAG⁻/⁻ mice against a lethal VACV-WR infection demonstrated that they are both necessary and sufficient in protecting against a primary VACV-WR infection of the respiratory tract.
针对呼吸道正痘病毒感染（如人类天花或猴痘）的精确免疫成分仍有待充分确定。在这项研究中，我们使用了强毒的西方储备株牛痘病毒（VACV-WR）来模拟原发性呼吸道正痘病毒感染。感染 VACV-WR 的新生小鼠产生了针对主要和次要 VACV-WR 抗原的早期 CD8 T 细胞反应，随后产生了 CD4 T 细胞和 Ig 反应。与其他强调 CD4 T 细胞和 Ig 关键作用的 VACV-WR 感染模型不同，我们发现只有缺乏 CD8 T 细胞的小鼠才会出现严重的恶病质、肺部炎症、病毒传播和 100%的死亡率。在感染过程中的特定时间点耗尽 CD8 T 细胞突出表明，它们在感染后第 4 天至第 6 天之间发挥关键作用，并且它们的保护需求受到初始病毒载量和毒力的严格控制。最后，过继转移的幼稚 CD8 T 细胞保护 Rag⁻/⁻小鼠免受致死性 VACV-WR 感染的能力证明，它们在保护呼吸道原发性 VACV-WR 感染方面是必要且充分的。
