Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland, Oregon, United States of America.
University of Portland, Department of Biology, Portland, Oregon, United States of America.
PLoS Pathog. 2023 Jan 23;19(1):e1010351. doi: 10.1371/journal.ppat.1010351. eCollection 2023 Jan.
CMV, a ubiquitous herpesvirus, elicits an extraordinarily large T cell response that is sustained or increases over time, a phenomenon termed 'memory inflation.' Remarkably, even latent, non-productive infection can drive memory inflation. Despite intense research on this phenomenon, the infected cell type(s) involved are unknown. To identify the responsible cell type(s), we designed a Cre-lox murine CMV (MCMV) system, where a spread-deficient (ΔgL) virus expresses recombinant SIINFEKL only in Cre+ host cells. We found that latent infection of endothelial cells (ECs), but not dendritic cells (DCs) or hepatocytes, was sufficient to drive CD8 T cell memory inflation. Infection of Lyve-1-Cre and Prox1-CreERT2 mice revealed that amongst EC subsets, infection of lymphatic ECs was sufficient. Genetic ablation of β2m on lymphatic ECs did not prevent inflation, suggesting another unidentified cell type can also present antigen to CD8 T cells during latency. This novel system definitively shows that antigen presentation by lymphatic ECs drives robust CD8 T cell memory inflation.
巨细胞病毒（CMV）是一种普遍存在的疱疹病毒，可引发极其强烈的 T 细胞反应，这种反应随着时间的推移而持续或增强，这一现象被称为“记忆膨胀”。值得注意的是，即使是潜伏的、非增殖性感染也能驱动记忆膨胀。尽管对这一现象进行了深入研究，但涉及的感染细胞类型仍不清楚。为了确定负责的细胞类型，我们设计了一个 Cre-lox 鼠巨细胞病毒（MCMV）系统，其中一种传播缺陷（ΔgL）病毒仅在 Cre+宿主细胞中表达重组 SIINFEKL。我们发现，内皮细胞（ECs）的潜伏感染足以驱动 CD8 T 细胞记忆膨胀，但树突状细胞（DCs）或肝细胞的潜伏感染则不足以驱动。Lyve-1-Cre 和 Prox1-CreERT2 小鼠的感染表明，在 EC 亚群中，淋巴管内皮细胞的感染就足以驱动记忆膨胀。在淋巴管内皮细胞上敲除β2m 并不能阻止膨胀，这表明在潜伏期间，另一种未被识别的细胞类型也可以向 CD8 T 细胞呈递抗原。这个新系统明确地表明，淋巴管内皮细胞的抗原呈递驱动了强烈的 CD8 T 细胞记忆膨胀。
