Actively induced antigen-specific CD8+ T cells by epitope-bearing parasite pre-infection but not prime/boost virus vector vaccination could ameliorate the course of Plasmodium yoelii blood-stage infection.
Actively induced antigen-specific CD8+ T cells by epitope-bearing parasite pre-infection but not prime/boost virus vector vaccination could ameliorate the course of Plasmodium yoelii blood-stage infection.
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通过携带表位的寄生虫感染前主动诱导抗原特异性 CD8 T 细胞，而不是初免/加强病毒载体疫苗接种，可以改善约氏疟原虫血期感染的过程。
DOI：
10.1016/j.vaccine.2012.08.009
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发表时间：
2012
期刊：
影响因子：
5.5
通讯作者：
Miyahira Y.
中科院分区：
文献类型：
--
作者：
Ono T;Yamaguchi Y;Oguma T;Takayama E;Takashima Y;Tadakuma T;Miyahira Y.
红细胞（rbc）上缺乏MHC分子导致了关于CD8+T细胞对疟疾血期（MBS）免疫功能的问题。然而，最近一些与这一概念相矛盾的报告表明，它们在MBS感染过程中起着重要作用。目前的研究产生了基因工程的小鼠疟疾，约利疟原虫，表达一个定义明确的克氏锥虫衍生的，h - 2kb限制性CD8+T细胞表位，ANYNFTLV。使用重组腺病毒和重组修饰的安卡拉牛痘病毒（MVA）进行Prime/boost疫苗接种，诱导了anynftlv特异性CD8+T细胞数量的增加，但未能阻止表达anynftlv的小鼠MBS感染发生病理结果。即使与相当数量的体外扩增的anynftlv特异性CD8+T细胞的被动转移相结合，这一结果也没有改变。相比之下，预先感染具有相同CD8+T细胞表位的克氏锥虫可显著提高表达anynftlv的疟疾感染小鼠的存活率，而非对照疟疾感染小鼠的存活率。这种保护作用被使用CD8+T细胞消耗单克隆抗体所消除。虽然仅在某些情况下观察到保护作用，但积极诱导抗原特异性CD8+T细胞可以改善MBS引起的病理。这是第一个表明抗原特异性CD8+T细胞的活性诱导应包括在针对MBS疫苗的开发中的研究。
The lack of MHC molecules on red blood cells (RBCs) has led to questions regarding the immunological function of CD8+T cells against malarial blood-stage (MBS). However, several recent reports contradicting with this concept have suggested that they play an important role in the course of MBS infection. The present study generated genetically engineered murine malaria, Plasmodium yoelii, which expresses a well-defined Trypanosoma cruzi-derived, H-2Kb-restricted CD8+T cell epitope, ANYNFTLV. Prime/boost vaccination by the use of recombinant adenovirus and recombinant modified vaccinia virus Ankara (MVA), which induced an enhanced number of ANYNFTLV-specific CD8+T cells, failed to prevent a pathological outcome to occur upon ANYNFTLV-expressing murine MBS infection. This outcome did not change even with the combination of passive transfer of an appreciable number of in vitro-expanded ANYNFTLV-specific CD8+T cells. In contrast, the pre-infection of mice with T. cruzi, which intrinsically bears the same CD8+T cell epitope significantly improved the survival of ANYNFTLV-expressing malaria-infected mice but not that of control malaria-infected ones. This protective effect was abrogated by the use of a CD8+T cell-depleting monoclonal antibody. Although the protective effect was observed only in certain situations, the actively induced antigen-specific CD8+T cells could ameliorate the pathologies caused by the MBS. This is the first study to implicate that the active induction of antigen-specific CD8+T cells should be included in the development of a vaccine against MBS.