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Immunoregulatory mechanisms for the hepatitis virus specific T cell response

肝炎病毒特异性 T 细胞反应的免疫调节机制

基本信息

批准号：
17590620
负责人：
KAKIMI Kazuhiro
金额：
$ 2.3万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590620/
关键词：
HBV CTL memory T cell vaccine regulatory T cell 抑制性T細胞 DNAワクチン

项目摘要

In this study, we demonstrated the new concept for the maintenance of memory T cell response. Memory T cells can persist for a long period of time by rejuvenation of T cell memory. Memory CD8+T cells generated during an immune response are long-lived and self-renewing, offering enhanced host protection against re-infection. However, how an antigen- specific population of memory T cells is maintained throughout repetitive infections over potentially a lifetime is not known. Here we investigated the generation and maintenance of antigen- specific CD8+T cells and revealed the new concept that showing dynamic turnover of an antigen-specific memory T cell population during repeated antigen challenge in vivo. We demonstrated that a primary response potentially occurs upon every recall response and find that the skewed T-cell receptor(TCR) repertoire of pre-existing memory T cells is partly corrected by diversity in a newly formed(primary) population. Importantly, memory T cells generated in a more recent antigen encounter expand more vigorously in a subsequent recall response. A primary response during re-challenge therefore restores both the TCR diversity and proliferative potential of the memory T cell population. These findings indicate that memory T cell populations evolve over multiple challenges, favoring memory T cells generated in more recent encounters, and suggest that these primary populations have essential roles in the perpetuation of antigen-specific T cell populations.

在这项研究中，我们展示了维持记忆T细胞反应的新概念。记忆T细胞可以通过恢复T细胞记忆而持续很长一段时间。在免疫应答过程中产生的记忆性CD8+T细胞是长寿的和自我更新的，提供增强的宿主保护以防止再次感染。然而，记忆T细胞的抗原特异性群体如何在可能的一生中的重复感染中维持尚不清楚。在这里，我们研究了抗原特异性CD8+T细胞的产生和维持，并揭示了在体内重复抗原攻击期间显示抗原特异性记忆T细胞群体的动态更新的新概念。我们证明了一个主要的反应可能会发生在每一个回忆反应，并发现倾斜的T细胞受体（TCR）库的预先存在的记忆T细胞的部分纠正的多样性，在一个新形成的（主要）人口。重要的是，在最近的抗原遭遇中产生的记忆T细胞在随后的回忆反应中更有力地扩增。因此，再激发期间的初级应答恢复记忆T细胞群的TCR多样性和增殖潜力。这些发现表明，记忆T细胞群体在多重挑战中进化，有利于在最近的遭遇中产生的记忆T细胞，并表明这些初级群体在抗原特异性T细胞群体的永久化中具有重要作用。