Graduate School of Infection Control Sciences, Kitasato University, Shirokane 5-9-1, Minato-ku, Tokyo 108-8641, Japan.
Viruses. 2021 Aug 11;13(8):1589. doi: 10.3390/v13081589.
A small fraction of HIV-1-infected T cells forms populations of latently infected cells when they are a naive T-cell subset or in transit to a resting memory state. Latently HIV-1-infected cells reside in lymphoid tissues and serve as viral reservoirs. However, whether they systemically recirculate in the body and re-enter the lymphoid nodes are unknown. Here, we employed two in-vitro cell coculture systems mimicking the lymphatic endothelium in lymph nodes and investigated the homing potential, specifically the transendothelial migration (TEM), of two latently HIV-1-infected cell lines (J1.1 and ACH-2). In trans-well coculture systems, J1.1 and ACH-2 showed higher TEM efficiencies than their parental uninfected and acutely infected cells. The efficiency of TEM was enhanced by the presence of stromal cells, such as HS-5 and fibroblastic reticular cells. In an in-vitro reconstituted, three-dimensional coculture system in which stromal cells are embedded in collagen matrices, J1.1 showed slightly higher TEM efficiency in the presence of HS-5. In accordance with these phenotypes, latently infected cells adhered to the endothelial cells more efficiently than uninfected cells. Together, our study showed that latently HIV-1-infected cells enhanced cell adhesion and TEM abilities, suggesting their potential for efficient homing to lymph nodes.
一小部分 HIV-1 感染的 T 细胞在成为幼稚 T 细胞亚群或处于静止记忆状态时，会形成潜伏感染细胞群体。潜伏感染的 HIV-1 细胞存在于淋巴组织中，是病毒储存库。然而，它们是否在体内系统性循环并重新进入淋巴结尚不清楚。在这里，我们采用了两种体外细胞共培养系统，模拟淋巴结中的淋巴内皮细胞，并研究了两种潜伏 HIV-1 感染细胞系（J1.1 和 ACH-2）的归巢潜力，特别是跨内皮迁移（TEM）。在 Trans-well 共培养系统中，J1.1 和 ACH-2 比其亲本未感染和急性感染细胞表现出更高的 TEM 效率。基质细胞（如 HS-5 和纤维状网状细胞）的存在增强了 TEM 的效率。在体外重建的三维共培养系统中，基质细胞嵌入胶原基质中，在 HS-5 的存在下，J1.1 表现出稍高的 TEM 效率。与这些表型一致，潜伏感染的细胞比未感染的细胞更有效地黏附在内皮细胞上。总之，我们的研究表明，潜伏感染的 HIV-1 细胞增强了细胞黏附和 TEM 能力，表明它们有潜力有效地归巢到淋巴结。
