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全细胞百日咳疫苗接种后,尽管反复进行无细胞加强剂接种,Th1/Th17 极化仍持续存在。

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters.

机构信息

Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology, La Jolla, California, USA.

Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA.

出版信息

J Clin Invest. 2018 Aug 31;128(9):3853-3865. doi: 10.1172/JCI121309. Epub 2018 Aug 6.

Abstract

In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-β and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.

摘要

在 20 世纪 90 年代中期,全细胞百日咳(wP)疫苗与局部和全身不良事件相关,这促使许多高收入国家用无细胞百日咳(aP)疫苗替代了 wP 疫苗。在过去的十年中,仅接受 aP 疫苗接种的儿童百日咳病的发病率有所增加。我们使用激活诱导标志物(AIM)检测,比较了接受 wP 或 aP 疫苗初始剂量的个体对 aP 加强剂的免疫反应。具体而言,我们检测了 ex vivo 百日咳特异性记忆 CD4+T 细胞反应,突出了 2 型/Th2 与 1 型/Th1 和 Th17 极化的差异,这是儿童接种疫苗的一个功能。值得注意的是,在接受现代 aP 加强剂后,最初用 aP 引发的供体的细胞与(a)增加的 IL-4、IL-5、IL-13、IL-9 和 TGF-β以及减少的 IFN-γ和 IL-17 产生相关,(b)在其 ex vivo 扩增记忆细胞的能力上存在缺陷,(c)在体外增殖能力较差。这些差异似乎是 T 细胞特异性的,因为在两组中都观察到 aP 加强后抗体滴度和浆母细胞的等效增加。总之,我们的数据表明,与最初接受 wP 的个体相比,最初接受 aP 疫苗接种的成年人的 T 细胞反应的极化和增殖存在持久的影响和差异,尽管反复接受了无细胞加强剂。

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