Mott Kevin R, Allen Sariah J, Zandian Mandana, Akbari Omid, Hamrah Pedram, Maazi Hadi, Wechsler Steven L, Sharpe Arlene H, Freeman Gordon J, Ghiasi Homayon
Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Burns & Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, United States of America.
PLoS One. 2014 Jan 27;9(1):e87617. doi: 10.1371/journal.pone.0087617. eCollection 2014.
CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC.
CD80在刺激T细胞及随后控制感染过程中发挥关键作用。为研究CD80对单纯疱疹病毒1型(HSV-1)感染的影响,我们构建了一种重组HSV-1病毒,该病毒表达两个拷贝的CD80基因以替代潜伏期相关转录本(LAT)。这种突变病毒(HSV-CD80)表达高水平的CD80,并且在兔皮肤细胞中的病毒复制动力学与对照病毒相似。与亲本病毒不同,这种表达CD80的重组病毒在未成熟树突状细胞(DC)中能高效复制。此外,未成熟DC对HSV-CD80感染的易感性是由CD80与DC上的PD-L1结合介导的。这种相互作用也导致T细胞活化显著增加。综上所述,这些结果表明,将CD80作为疫苗佐剂可能通过直接增强免疫反应以及通过靶向DC间接增强免疫反应来提高疫苗效力。