Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections
Harnessing the antibacterial and immunological properties of mucosal-associated invariant T cells in the development of novel oral vaccines against enteric infections
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DOI：
10.1016/j.bcp.2014.08.017
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发表时间：
2014-11-15
影响因子：
5.8
通讯作者：
Lavelle, Ed C.
中科院分区：
文献类型：
--
作者：
Abautret-Daly, Aine E.;Davitt, Christopher J. H.;Lavelle, Ed C.
肠道感染是造成死亡和发病的主要原因，在世界范围内，特别是在发展中国家具有重大的社会和经济影响。减少这些疾病影响的一个有吸引力的办法是制定口服疫苗接种战略。然而，由于存在于胃肠道的抗原呈递细胞的耐受性和低反应性，口服疫苗接种具有挑战性。在口服疫苗制剂中加入佐剂有可能克服这一挑战。迄今为止，还没有口服佐剂获准用于人类，因此口服佐剂的发现仍然是提高口服疫苗开发潜力的关键目标。粘膜相关不变性T细胞（MAIT）是最近发现的一种非常规T细胞，其特征是进化上保守的α - β T细胞受体（TCR），该受体识别主要组织相容性复合体（MHC） i类相关（MR1）分子呈递的抗原。MAIT细胞通过表达MR1的双阳性胸腺细胞在胸腺内被选中，并以初始表型进入循环。在循环中，它们形成一种记忆表型，并被编程为粘膜组织和肝脏的家园。一旦进入这些组织，MAIT细胞通过产生趋化因子和细胞因子对细菌和酵母菌感染做出反应，这些趋化因子和细胞因子有助于诱导适应性免疫反应。它们在胃肠道中的丰度和促进适应性免疫的能力表明，MAIT细胞激活剂可能是用于口服疫苗接种的有吸引力的新型佐剂。(C) 2014爱思唯尔公司版权所有。
Enteric infections are a major cause of mortality and morbidity with significant social and economic implications worldwide and particularly in developing countries. An attractive approach to minimizing the impact of these diseases is via the development of oral vaccination strategies. However, oral vaccination is challenging due to the tolerogenic and hyporesponsive nature of antigen presenting cells resident in the gastrointestinal tract. The inclusion of adjuvants in oral vaccine formulations has the potential to overcome this challenge. To date no oral adjuvants have been licenced for human use and thus oral adjuvant discovery remains a key goal in improving the potential for oral vaccine development. Mucosal-associated invariant T (MAIT) cells are a recently discovered population of unconventional T cells characterized by an evolutionarily conserved alpha beta T cell receptor (TCR) that recognizes antigens presented by major histocompatibility complex (MHC) class I-related (MR1) molecule. MAIT cells are selected intra-thymically by MR1 expressing double positive thymocytes and enter the circulation with a naive phenotype. In the circulation they develop a memory phenotype and are programmed to home to mucosal tissues and the liver. Once resident in these tissues, MAIT cells respond to bacterial and yeast infections through the production of chemokines and cytokines that aid in the induction of an adaptive immune response. Their abundance in the gastrointestinal tract and ability to promote adaptive immunity suggests that MAIT cell activators may represent attractive novel adjuvants for use in oral vaccination. (C) 2014 Elsevier Inc. All rights reserved.