(S.R.S.) I was introduced to viral immunology while working in Peter Doherty's laboratory in the early stages of my research career, inspiring a lifelong interest in this area. During those early years under Peter's mentorship, we studied a mouse gammaherpesvirus model (murine gammaherpesvirus-68 [MHV-68]) that provided a useful small animal model for investigating the immunological control of gammaherpesvirus infection. Interestingly, while CD4 T cells were not required for acute control of MHV-68 in the lung, CD8 T cell-mediated control was progressively lost in the absence of CD4 T cell help, leading to viral recrudescence. This was one of several early studies showing that CD8 T cell control of persistent viral infections was lost in the absence of CD4 T cell help, preceding the concept of CD8 T cell exhaustion. Further studies showed that MHV-68 infection of mice offered a unique model for comparing the mechanisms of acute and long-term control of a persistent viral infection and developing strategies for reversing T cell exhaustion. Here, we provide a brief review of the literature on CD8 T cell activation and exhaustion in this model, focusing on the role of CD40 and B7 family members and including some previously unpublished data.

中文翻译：

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从小鼠 Gammaherpes 病毒模型深入了解 CD8 T 细胞激活和耗竭。

(SRS) 在我研究生涯的早期阶段，我在 Peter Doherty 的实验室工作时接触了病毒免疫学，激发了我对这一领域的终生兴趣。在 Peter 的指导下的那些早年，我们研究了小鼠 gammaherpesvirus 模型（小鼠 gammaherpesvirus-68 [MHV-68]），该模型为研究 gammaherpesvirus 感染的免疫控制提供了一个有用的小动物模型。有趣的是，虽然 CD4 T 细胞不需要急性控制肺部 MHV-68，但在没有 CD4 T 细胞帮助的情况下，CD8 T 细胞介导的控制逐渐丧失，导致病毒复发。这是几项早期研究之一，表明在 CD8 T 细胞耗竭概念出现之前，如果没有 CD4 T 细胞的帮助，CD8 T 细胞对持续性病毒感染的控制就会丧失。进一步的研究表明，小鼠的 MHV-68 感染提供了一个独特的模型，用于比较持续病毒感染的急性和长期控制机制以及制定逆转 T 细胞耗竭的策略。在这里，我们简要回顾了关于该模型中 CD8 T 细胞激活和耗竭的文献，重点关注 CD40 和 B7 家族成员的作用，并包括一些以前未发表的数据。