Wuchang Hospital, Affiliated to Wuhan University of Science and Technology, Wuhan, China.
Department of Clinical Laboratory, Wuhan Fourth Hospital, Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Immunol. 2019 May 7;10:1022. doi: 10.3389/fimmu.2019.01022. eCollection 2019.
The present study evaluated the impact of blocking cytotoxic T-lymphocyte antigen-4 (CTLA-4) activity on the protective effect elicited by the fatty acid binding protein (FABP) vaccine against infection. Mice were randomly divided into uninfected, infected control, anti-CTLA-4 monoclonal antibody (anti-CTLA-4 mAb), FABP, and combination (anti-CTLA-4 mAb and FABP) groups. An assessment of the worm and egg burden in the infected mice revealed that the worm reduction-rate induced by FABP administration was increased from 26.58 to 54.61% by co-administration of the monoclonal anti-CTLA antibody (anti-CTLA-4 mAb). Furthermore, the regulatory T cell (Treg) percentage was significantly increased in mice after administration of the anti-CTLA-4 mAb, but not the FABP vaccine, and elevated levels of the cytokines interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-5 were observed in infected mice that were administered the anti-CTLA-4 mAb. Notably, the diameter of egg granulomas in the anti-CTLA-4 mAb and combination groups was significantly increased compared to that observed in the infected control group. Together, these results suggest that co-administering the FABP vaccine and anti-CTLA-4 treatment may have synergistically increased the immunoprotective effect of the FABP vaccine by promoting T-helper 1-type immune responses, while incurring increased tissue damage.
本研究评估了阻断细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）活性对脂肪酸结合蛋白（FABP）疫苗预防 感染的保护作用的影响。将小鼠随机分为未感染组、感染对照组、抗 CTLA-4 单克隆抗体（抗 CTLA-4 mAb）组、FABP 组和联合（抗 CTLA-4 mAb 和 FABP）组。评估感染小鼠中的 虫体和卵负荷发现，FABP 给药时诱导的虫体减少率由单独给药时的 26.58%增加到 54.61%，同时联合使用抗 CTLA-4 mAb。此外，抗 CTLA-4 mAb 给药后调节性 T 细胞（Treg）的比例显著增加，但 FABP 疫苗没有，并且在感染小鼠中观察到干扰素（IFN）-γ、白细胞介素（IL）-2、IL-4 和 IL-5 等细胞因子水平升高。值得注意的是，与感染对照组相比，抗 CTLA-4 mAb 组和联合组的卵肉芽肿直径显著增加。综上所述，FABP 疫苗和抗 CTLA-4 联合治疗可能通过促进 Th1 型免疫反应协同增强 FABP 疫苗的免疫保护作用，同时导致组织损伤增加。
