Immunoregulatory mechanisms for the hepatitis virus specific T cell response

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。在免疫反应过程中产生的记忆CD8+T细胞是长期生存和自我更新的，提供增强的宿主保护，防止再次感染。然而，抗原特异的记忆T细胞群体是如何在重复感染过程中保持终生的尚不清楚。在这里，我们研究了抗原特异性CD8+T细胞的产生和维持，并揭示了在体内反复抗原攻击时抗原特异性记忆T细胞群体的动态更替的新概念。我们证明了每个回忆反应都可能发生初级反应，并发现新形成的(初级)群体中的多样性部分纠正了先前存在的记忆T细胞的扭曲的T细胞受体(TCR)谱系。重要的是，在最近的一次抗原遭遇中产生的记忆T细胞在随后的回忆反应中会更有力地扩张。因此，在重新挑战期间的主要反应恢复了记忆T细胞群体的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起着至关重要的作用。

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.