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首页> 外文期刊>Infection and immunity >CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of Bacillus anthracis Lethal Toxin-Neutralizing Antibodies
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CD1d-Dependent B-Cell Help by NK-Like T Cells Leads to Enhanced and Sustained Production of Bacillus anthracis Lethal Toxin-Neutralizing Antibodies

机译：NK样T细胞对CD1d依赖性B细胞的帮助导致炭疽杆菌致死毒素中和抗体的增强和持续生产。

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The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (α-galactosylceramide [α-GC]) at the time of immunization improves PA-specific Ab responses. We observed that α-GC enhanced PA-specific Ab titers in C57BL/6 mice. In CD1d?/? mice deficient in type I and type II NKT cells the anti-PA Ab response was diminished. In Jα281?/? mice expressing CD1d but lacking type I α-GC-reactive NKT cells, α-GC did not enhance the Ab response. In vitro neutralization assays were performed and showed that the Ab titers correlated with protection of macrophages against anthrax lethal toxin (LT). The neutralization capacity of the Ab was further tested in lethal challenge studies, which revealed that NKT activation leads to enhanced in vivo protection against LT. Anti-PA Ab titers, neutralization, and protection were then measured over a period of several months, and this revealed that NKT activation leads to a sustained protective Ab response. These results suggest that NKT-activating CD1d ligands could be exploited for the development of improved vaccines for Bacillus anthracis that increase not only neutralizing Ab titers but also the duration of the protection afforded by Ab.
机译：当前的炭疽芽孢杆菌疫苗主要由保护性抗原（PA）组成，它是介导水肿因子（EF）或致死因子（LF）进入细胞的炭疽毒素蛋白。 PA诱导抗炭疽芽孢杆菌的保护性抗体（Ab）介导的免疫，但功效和持续时间有限。我们以前证明用CD1d结合糖脂激活CD1d限制性的自然杀手样T细胞（NKT）会导致特异于外源抗原（Ag）的Ab效价提高。因此，我们测试了以下假设：免疫时用CD1d配体（α-半乳糖基神经酰胺[α-GC]）激活NKT细胞可改善PA特异性Ab反应。我们观察到，α-GC增强了C57BL / 6小鼠的PA特异性Ab效价。在CD1d中？ I型和II型NKT细胞不足的小鼠，抗PA Ab反应减弱。在Jα281中？表达CD1d但缺乏I型α-GC反应性NKT细胞的小鼠，α-GC不能增强Ab反应。进行了体外中和测定，结果表明抗体滴度与巨噬细胞对炭疽致死毒素（LT）的保护有关。在致命攻击研究中进一步测试了抗体的中和能力，该研究表明NKT激活可增强体内对LT的保护作用。然后在几个月的时间内测量抗PA Ab的滴度，中和和保护作用，这表明NKT激活导致持续的保护性Ab反应。这些结果表明，NKT激活CD1d配体可用于开发炭疽芽孢杆菌的改良疫苗，这种疫苗不仅增加中和抗体的效价，而且增加抗体的保护时间。

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