Saikh Kamal U, Kissner Teri L, Nystrom Steven, Ruthel Gordon, Ulrich Robert G
Department of Immunology, Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA.
Clin Vaccine Immunol. 2008 Jan;15(1):131-7. doi: 10.1128/CVI.00320-07. Epub 2007 Nov 28.
Interleukin-15 (IL-15) is generally considered to sustain T-cell memory and to be a growth factor for natural killer cells. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. For this study, we investigated the effects of IL-15 on antibody responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax) in a preclinical model of toxic shock syndrome induced by SEB. We observed that mouse spleen cells treated with IL-15 in ex vivo culture gained a dendritic cell-like phenotype. Administration of IL-15 to mice also resulted in an increased number of mature CD11c+ dendritic cells in mouse spleens. A significant, IL-15 dose-dependent increase in antigen-specific antibody was observed after coadministration with the vaccine and an aluminum-based adjuvant (alhydrogel). Furthermore, the coadministration of IL-15 with STEBVax and alhydrogel also protected mice from lethal toxic shock above the levels that obtained without IL-15. Thus, the vaccine response enhanced by IL-15 appears to be mediated by mature dendritic cells and results in prevalent seroconversion to Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines.
白细胞介素-15（IL-15）通常被认为可维持T细胞记忆，并且是自然杀伤细胞的生长因子。我们实验室之前的数据表明，IL-15也是人类树突状细胞发育的重要因素。在本研究中，我们在由葡萄球菌肠毒素B（SEB）诱导的中毒性休克综合征临床前模型中，研究了IL-15对小鼠针对重组葡萄球菌肠毒素B疫苗（STEBVax）的抗体反应的影响。我们观察到，体外培养中用IL-15处理的小鼠脾细胞获得了树突状细胞样表型。给小鼠施用IL-15还导致小鼠脾脏中成熟CD11c +树突状细胞数量增加。与疫苗和铝基佐剂（氢氧化铝凝胶）共同施用后，观察到抗原特异性抗体有显著的、IL-15剂量依赖性增加。此外，IL-15与STEBVax和氢氧化铝凝胶共同施用还可使小鼠免受致命性中毒性休克，其保护水平高于未使用IL-15时。因此，IL-15增强的疫苗反应似乎由成熟树突状细胞介导，并导致普遍的血清转化为Th2依赖性抗体。这表明IL-15作为疫苗抗体依赖性反应佐剂的潜在用途。
