口服减毒伤寒疫苗Ty21a免疫后人体中针对伤寒沙门氏菌伤寒血清型、甲型副伤寒沙门氏菌和乙型副伤寒沙门氏菌的交叉反应多功能CD4+ T细胞应答
Cross-reactive multifunctional CD4+ T cell responses against Salmonella enterica serovars Typhi, Paratyphi A and Paratyphi B in humans following immunization with live oral typhoid vaccine Ty21a.
作者信息
Wahid Rezwanul, Fresnay Stephanie, Levine Myron M, Sztein Marcelo B
机构信息
Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Department of Pediatrics, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Medicine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
出版信息
Clin Immunol. 2016 Dec;173:87-95. doi: 10.1016/j.clim.2016.09.006. Epub 2016 Sep 12.
The live oral typhoid vaccine Ty21a elicits predominantly CD8+, as well as CD4+ T cells mediated immune responses. Clinical field studies showed that Ty21a is moderately effective against S. Typhi and S. Paratyphi B, but not S. Paratyphi A infections. In this study we describe the in depth characterization of S. Typhi, S. Paratyphi A and S. Paratyphi B cross-reactive CD4+ T cell responses elicited following immunization with Ty21a. PBMC samples were collected from 16 healthy volunteers before and 42/84days after Ty21a immunization and stimulated ex-vivo with Salmonella-infected targets. Multiparametric flow cytometry was used to detect the vaccine elicited Salmonella-specific responses in T effector/memory (T) and CD45RA+ T effector/memory (T) CD4+ cell subsets, by measuring CD4+ multifunctional (MF) cells that concomitantly produced IFN-γ, TNF-α, IL-2, MIP-1β, IL-17A and/or expressed CD107a. Post-vaccination increases in S. Typhi-specific MF cells were observed in CD4+ T and T subsets which predominantly produced IFN-γ and/or TNF-α, while IL-2 was produced by a smaller cell subset. A small proportion of those MF cells also produced MIP-1β, IL-17A and expressed CD107a (a marker associated with cytotoxicity). Approximately one third of these specific MF cells have the potential to migrate to the gut mucosa, as evidenced by co-expression of the gut-homing molecule integrin αβ. In contrast to our previous observations with CD8+ T cells, MF CD4+ T cell responses to the different Salmonella serovars evaluated were similar in magnitude and characteristics. We conclude that although induction of cross-reactive CD4+ MF effector T cells suggest a possible role in Salmonella-immunity, these responses are unlikely to provide an immunological basis for the observed efficacy of Ty21a against S. Typhi and S. Paratyphi B, but not to S. Paratyphi A.
口服伤寒活菌疫苗Ty21a主要引发CD8⁺以及CD4⁺T细胞介导的免疫反应。临床现场研究表明，Ty21a对伤寒沙门菌和副伤寒沙门菌B有一定疗效，但对副伤寒沙门菌A感染无效。在本研究中，我们描述了用Ty21a免疫后引发的伤寒沙门菌、副伤寒沙门菌A和副伤寒沙门菌B交叉反应性CD4⁺T细胞反应的深入特征。在Ty21a免疫前和免疫后42/84天从16名健康志愿者收集外周血单个核细胞（PBMC）样本，并在体外用感染沙门菌的靶细胞进行刺激。通过测量同时产生干扰素-γ、肿瘤坏死因子-α、白细胞介素-2、巨噬细胞炎性蛋白-1β、白细胞介素-17A和/或表达CD107a的CD4⁺多功能（MF）细胞，采用多参数流式细胞术检测疫苗在T效应/记忆（T）和CD45RA⁺T效应/记忆（T）CD4⁺细胞亚群中引发的沙门菌特异性反应。接种疫苗后，在主要产生干扰素-γ和/或肿瘤坏死因子-α的CD4⁺T和T亚群中观察到伤寒沙门菌特异性MF细胞增加，而白细胞介素-2由较小的细胞亚群产生。这些MF细胞中有一小部分还产生巨噬细胞炎性蛋白-1β、白细胞介素-17A并表达CD107a（一种与细胞毒性相关的标志物）。这些特异性MF细胞中约三分之一有可能迁移到肠道黏膜，肠道归巢分子整合素αβ的共表达证明了这一点。与我们之前对CD8⁺T细胞的观察结果相反，评估的不同沙门菌血清型的MF CD4⁺T细胞反应在强度和特征上相似。我们得出结论，虽然交叉反应性CD4⁺MF效应T细胞的诱导表明其在沙门菌免疫中可能起作用，但这些反应不太可能为观察到的Ty21a对伤寒沙门菌和副伤寒沙门菌B有效而对副伤寒沙门菌A无效提供免疫学基础。
Zotero 插件