Key Points Perforin is a dominant control mechanism of B lymphoma in γHV infection. Immune effector hierarchies differ in control of B lymphoma and γHV replication. CD4 T cell help is not essential to control B lymphoma in γHV immune mice. Persistent infection with gammaherpesviruses (γHV) can cause lymphomagenesis in immunocompromised patients. Murine γHV-68 (MHV-68) is an important tool for understanding immune factors contributing to γHV control; however, modeling control of γHV-associated lymphomagenesis has been challenging. Current model systems require very long incubation times or severe immune suppression, and tumor penetrance is low. In this report, we describe the generation of a B cell lymphoma on the C57BL/6 background, which is driven by the Myc oncogene and expresses an immunodominant CD8 T cell epitope from MHV-68. We determined MHV-68–specific CD8 T cells in latently infected mice use either IFN-γ or perforin/granzyme to control γHV-associated lymphoma, but perforin/granzyme is a more potent effector mechanism for lymphoma control than IFN-γ. Consistent with previous reports, CD4-depleted mice lost control of virus replication in persistently infected mice. However, control of lymphoma remained intact in the absence of CD4 T cells. Collectively, these data show the mechanisms of T cell control of B cell lymphoma in γHV-infected mice overlap with those necessary for control of virus replication, but there are also important differences. This study establishes a tool for further dissecting immune surveillance against, and optimizing adoptive T cell therapies for, γHV-associated lymphomas.

中文翻译：

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伽玛疱疹病毒诱导的记忆 CD8 T 细胞控制 B 细胞淋巴瘤

要点 穿孔素是 γHV 感染中 B 淋巴瘤的主要控制机制。免疫效应器层次在 B 淋巴瘤和 γHV 复制的控制方面有所不同。CD4 T 细胞的帮助对于控制 γHV 免疫小鼠的 B 淋巴瘤并不是必需的。伽玛疱疹病毒（γHV）的持续感染可导致免疫功能低下患者发生淋巴瘤。鼠 γHV-68 (MHV-68) 是了解有助于 γHV 控制的免疫因素的重要工具；然而，γHV 相关淋巴瘤发生的建模控制一直具有挑战性。目前的模型系统需要很长的孵育时间或严重的免疫抑制，并且肿瘤外显率较低。在本报告中，我们描述了 C57BL/6 背景下 B 细胞淋巴瘤的产生，该淋巴瘤由 Myc 癌基因驱动，并表达来自 MHV-68 的免疫显性 CD8 T 细胞表位。我们确定潜伏感染小鼠中的 MHV-68 特异性 CD8 T 细胞使用 IFN-γ 或穿孔素/颗粒酶来控制 γHV 相关淋巴瘤，但穿孔素/颗粒酶是比 IFN-γ 更有效的淋巴瘤控制效应机制。与之前的报道一致，CD4 缺失的小鼠在持续感染的小鼠中失去了对病毒复制的控制。然而，在缺乏 CD4 T 细胞的情况下，淋巴瘤的控制仍然完好无损。总的来说，这些数据表明，γHV 感染小鼠中 T 细胞控制 B 细胞淋巴瘤的机制与控制病毒复制所需的机制重叠，但也存在重要差异。这项研究建立了一种工具，用于进一步剖析针对 γHV 相关淋巴瘤的免疫监视，并优化过继性 T 细胞疗法。