Department of Microbiology and Immunology, Cornell University, Ithaca, NY.
J Immunol. 2024 Oct 1;213(7):933-939. doi: 10.4049/jimmunol.2400150.
The most common congenital viral infection is CMV, which leads to numerous neurologic disabilities. Using a mouse model of congenital CMV, we previously determined that Ag-specific CD8+ T cells traffic to the brain in a CCR9-dependent manner. The mechanism by which these CD8+ T cells acquire a CCR9-dependent "brain-tropic" phenotype remains unclear. In this study, we identify the key factor that imprints brain homing specificity on CD8+ T cells, the source of production, and the location where CCR9 expression is induced. Specifically, we discovered that CCR9 is induced on CD8+ T cells by retinoic acid-producing CD8α+ dendritic cells in the cervical lymph node postinfection. We found that retinoic acid is important for CD8+ T cells to establish tissue residency in the brain. Collectively, our data expand the role of retinoic acid during infection and mechanistically demonstrate how CD8+ T cells are primed to protect the brain during congenital viral infection.
最常见的先天性病毒感染是 CMV，它会导致许多神经残疾。我们之前使用先天性 CMV 的小鼠模型确定，Ag 特异性 CD8+ T 细胞以 CCR9 依赖的方式转移到大脑。这些 CD8+ T 细胞获得 CCR9 依赖性“嗜脑”表型的机制尚不清楚。在这项研究中，我们确定了在 CD8+ T 细胞上印上脑归巢特异性、产生的来源以及诱导 CCR9 表达的位置的关键因素。具体来说，我们发现感染后，颈淋巴结中的产生视黄酸的 CD8α+树突状细胞诱导 CD8+ T 细胞表达 CCR9。我们发现视黄酸对于 CD8+ T 细胞在大脑中建立组织驻留是重要的。总之，我们的数据扩展了视黄酸在感染过程中的作用，并从机制上证明了 CD8+ T 细胞如何在先天性病毒感染期间被激活以保护大脑。
