Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Research Foundation , Cincinnati, OH , USA ; Immunology Graduate Program, College of Medicine, University of Cincinnati , Cincinnati, OH , USA.
Institute for Virology, University Hospital Essen, University Duisburg-Essen , Essen , Germany.
Front Immunol. 2014 May 8;5:199. doi: 10.3389/fimmu.2014.00199. eCollection 2014.
Formation of immunological synapses (IS) between dendritic cells (DCs) and conventional CD4(+) T cells (Tcon) is critical for productive immune responses. However, when DCs are HIV-infected such synapses are critical to establish HIV infection. As regulatory T cells (Treg) control DC-Tcon interactions, we inquired whether Treg might interfere with DC to Tcon HIV infection. We developed a model, using monocyte-derived DC infected with R5-HIV, and cultured with Tcon in the presence or absence of autologous Treg, using the physiological ratio of 1 Treg for 10 Tcon. Cultures containing Treg significantly decreased HIV infection in DC:T cell clusters. Notably, Treg appear to have an effect on the quality of the IS, as Treg decreased actin polymerization and DC maturation. Importantly, Treg decreased the trafficking of HIV punctate to the IS. Further, CD152 and cyclic adenosine monophosphate were critical Treg effector molecules, as their individual or simultaneous blockade abolished Treg activity, however no additive effect was found. Together, these data suggest that Treg can reduce HIV dissemination, which may be beneficial to the host in the early stages of infection.
免疫突触(IS)在树突状细胞(DC)和传统的 CD4(+) T 细胞(Tcon)之间的形成对于有效的免疫反应至关重要。然而,当 DC 感染 HIV 时,这种突触对于建立 HIV 感染至关重要。由于调节性 T 细胞(Treg)控制 DC-Tcon 相互作用,我们询问 Treg 是否可能干扰 DC 向 Tcon 的 HIV 感染。我们开发了一种模型,使用单核细胞衍生的 DC 感染 R5-HIV,并在存在或不存在自体 Treg 的情况下与 Tcon 共培养,使用 1 Treg 对 10 Tcon 的生理比例。含有 Treg 的培养物显著降低了 DC:T 细胞簇中的 HIV 感染。值得注意的是,Treg 似乎对 IS 的质量有影响,因为 Treg 减少了肌动蛋白聚合和 DC 成熟。重要的是,Treg 减少了 HIV 点状物质向 IS 的转运。此外,CD152 和环磷酸腺苷是关键的 Treg 效应分子,因为它们的单独或同时阻断消除了 Treg 的活性,但没有发现附加效应。总之,这些数据表明 Treg 可以减少 HIV 的传播,这可能对感染早期的宿主有益。