The recombinant tuberculosis vaccine rBCG ΔureC::hly+ induces apoptotic vesicles for improved priming of CD4+ and CD8+ T cells
The recombinant tuberculosis vaccine rBCG ΔureC::hly+ induces apoptotic vesicles for improved priming of CD4+ and CD8+ T cells
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DOI：
10.1016/j.vaccine.2012.10.031
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发表时间：
2012-12-14
期刊：
影响因子：
5.5
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
--
作者：
Farinacci, Maura;Weber, Stephan;Kaufmann, Stefan H. E.
背景：在临床前模型中，重组BCG Delta UREC：：HLY(+)(RBCG)候选疫苗比亲本BCG(PBCG)更有效地对抗结核病(TB)。有证据表明存在更好的CD4和CD8 T细胞刺激。尽管相关的免疫机制还不完全清楚，但CD8T细胞的交叉交叉已被认为是rBCG比PBCG更好保护的主要机制。本研究探讨了PBCG和rBCG感染的巨噬细胞中的凋亡小泡在交叉杂交中的作用。方法：分离PBCG和rBCG感染的小鼠巨噬细胞中的凋亡小泡。结果：PBCG和rBCG感染的巨噬细胞的凋亡囊泡均能激活树突状细胞，但激活程度不同。总体而言，与pBCG相比，rBCG感染的凋亡小泡诱导了更深刻的CD4和CD8T细胞反应。结论：这些数据支持这样的观点，即rBCG疫苗效力的提高依赖于更强的细胞凋亡导致的增强的交叉反应。(C)2012爱思唯尔有限公司。保留所有权利。
Background: The recombinant BCG Delta ureC::hly(+) (rBCG) vaccine candidate is more efficient than parental BCG (pBCG) against tuberculosis (TB) in preclinical models. Evidence exists for superior CD4 and CD8 T cell stimulation. Although the responsible immune mechanisms are incompletely understood, crosspriming of CD8 T cells has been proposed as a major mechanism underlying better protection of rBCG over pBCG. The present study investigates the role of apoptotic vesicles from pBCG- and rBCG-infected macrophages in crosspriming.Methods: Apoptotic vesicles were isolated from pBCG- and rBCG-infected mouse macrophages. The priming potential of the isolated vesicles was evaluated in terms of dendritic cell activation and specific T cell stimulation.Results: Apoptotic vesicles from both pBCG- and rBCG-infected macrophages activated dendritic cells but to a different degree. Overall, rBCG-infected apoptotic vesicles induced more profound CD4 and CD8 T cell responses as compared to pBCG.Conclusions: These data support the notion that the improved vaccine efficacy of rBCG rests on enhanced crosspriming as a consequence of stronger apoptosis. (C) 2012 Elsevier Ltd. All rights reserved.