Key Points Clonal stability is a feature of memory inflation. Stochastic expansions maintain clonal stability during memory inflation. Persistent clonotypes are often public in the context of memory inflation. CMV is an obligate and persistent intracellular pathogen that continually drives the production of highly differentiated virus-specific CD8+ T cells in an Ag-dependent manner, a phenomenon known as memory inflation. Extensive proliferation is required to generate and maintain inflationary CD8+ T cell populations, which are counterintuitively short-lived and typically exposed to limited amounts of Ag during the chronic phase of infection. An apparent discrepancy therefore exists between the magnitude of expansion and the requirement for ongoing immunogenic stimulation. To address this issue, we explored the clonal dynamics of memory inflation. First, we tracked congenically marked OT-I cell populations in recipient mice infected with murine CMV (MCMV) expressing the cognate Ag OVA. Irrespective of numerical dominance, stochastic expansions were observed in each population, such that dominant and subdominant OT-I cells were maintained at stable frequencies over time. Second, we characterized endogenous CD8+ T cell populations specific for two classic inflationary epitopes, M38 and IE3. Multiple clonotypes simultaneously underwent Ag-driven proliferation during latent infection with MCMV. In addition, the corresponding CD8+ T cell repertoires were stable over time and dominated by persistent clonotypes, many of which also occurred in more than one mouse. Collectively, these data suggest that stochastic encounters with Ag occur frequently enough to maintain oligoclonal populations of inflationary CD8+ T cells, despite intrinsic constraints on epitope display at individual sites of infection with MCMV.

中文翻译：

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随机扩张维持 CD8+ T 细胞群的克隆稳定性，这些细胞群经历了由鼠巨细胞病毒驱动的记忆膨胀

要点 克隆稳定性是内存膨胀的一个特征。随机扩张在记忆膨胀期间保持克隆稳定性。在记忆膨胀的背景下，持久性克隆型通常是公开的。CMV 是一种专性且持久的细胞内病原体，它以 Ag 依赖性方式持续驱动高度分化的病毒特异性 CD8+ T 细胞的产生，这种现象称为记忆膨胀。需要大量增殖来产生和维持膨胀的 CD8+ T 细胞群，这些细胞群的寿命违反直觉，并且通常在感染的慢性阶段暴露于有限量的 Ag。因此，扩增幅度与持续免疫原性刺激的需求之间存在明显差异。为了解决这个问题，我们探索了记忆膨胀的克隆动力学。首先，我们在感染了表达同源 Ag OVA 的鼠类 CMV (MCMV) 的受体小鼠中追踪了同源标记的 OT-I 细胞群。不考虑数量优势，在每个群体中都观察到随机扩张，使得优势和次优势 OT-I 细胞随着时间的推移保持稳定的频率。其次，我们表征了对两个经典膨胀表位 M38 和 IE3 具有特异性的内源性 CD8+ T 细胞群。在 MCMV 潜伏感染期间，多个克隆型同时经历 Ag 驱动的增殖。此外，相应的 CD8+ T 细胞库随着时间的推移是稳定的，并以持久性克隆型为主，其中许多也发生在不止一只小鼠身上。总的来说，