Memory Tfh

发表于 分类于 ， ， 阅读次数： 本文字数： 1.3k 阅读时长 ≈ 5 分钟

Memory Tfh

💡 Meta Data

Title: Memory T Follicular Helper CD4 T Cells

Journal: Frontiers in Immunology

Authors: J. Scott Hale; Rafi Ahmed

Pub.date: 2015

DOI: 10.3389/fimmu.2015.00016

📜 研究背景 & 基础 & 目的

  • Tfh的身份，功能，特征总结

    “T follicular helper (Tfh) cells are the subset of CD4T helper cells that are required for generation and maintenance of germinal center reactions and the generation of long-lived humoral immunity. This specialized T helper subset provides help to cognate B cells via their expression of CD40 ligand, IL-21, IL-4, and other molecules. Tfh cells are characterized by their expression of the chemokine receptor CXCR5, expression of the transcriptional repressor Bcl6, and their capacity to migrate to the follicle and promote germinal center B cell responses.”

  • “Tfh cells play a critical role in the generation of effective and long-lived humoral immune responses to antigens”

  • Th1与Th2的Signature

    “Th1 signature cytokine IFNγ or the Th2 cytokines IL-4, IL-5, and IL-13”

  • BCL6是Tfh产生维持所必需的，也促进了Tfh的分化，部分是通过抑制转录调节因子 Tbet、RORγt、GATA3

    和 PRDM1的转录

📊 研究内容

  • 记忆T细胞相比NaiveT的优势

    • 抗原特异性记忆细胞的数量相对于其幼稚的抗原特异性前体而言有所增加，从而提供更好的覆盖范围和对病原体再攻击的更快速的细胞反应。
    • 其次，记忆细胞并不局限于血液循环和次级淋巴器官，而是还可以运输并驻留在非淋巴组织中，如果它们的特定病原体进入该特定解剖部位，它们可以在非淋巴组织中迅速发挥效应功能。
    • 记忆 T 细胞在细胞内在编程方面发生了变化，使它们能够快速回忆起它们的效应功能，例如特定效应细胞因子、趋化因子和细胞毒性分子的快速表达
    • 寿命更

  • 问题

    • First, do Tfh cells survive to become memory cells?
    • Second, do memory cells derived from Tfh cells maintain their commitment/programing to recall Tfh effector cells？
    • Third, instead possess pluripotency/plasticity to become cells of other T helper lineages?

  • Tfh并非注定死亡，而是有部分发展成为记忆细胞

    “Together, these studies clearly demonstrate that not all Tfh effector cells are terminally differentiated and fated to die. Instead, some Tfh effector cells progress to become memory cells that have some similar features compared to their Tfh effector predecessors.”

  • 记忆Tfh细胞形成有两种模型

    • Lineage Commitment Model
    • Degrees of Commitment Model

  • 记忆Tfh细胞恢复自己的记忆可能存在四种潜在的机制

    • cell-intrinsic programs
    • Tfh associated transcription factors
    • Localization and trafficking
    • Epigenetic regulation

🚩 研究结论

  • 表型独特的 CXCR5+ 记忆 CD4 T 细胞亚群具有特定于 Tfh 功能的记忆潜力这一发现引发了未来研究的重要问题，这些研究将为传染病的疫苗接种策略提供信息。
  • 了解 Tfh 记忆细胞如何获得和保存 Tfh 基因表达程序并在重新激活时优先回忆这些程序的机制将为了解这些细胞的谱系维持和可塑性提供重要的见解。
  • 最后，未来的工作需要确定在初免和加强免疫期间利用 Tfh 记忆细胞的最佳方法，以促进提高保护性和长寿命抗体反应的方法

📌 感想 & 疑问

🔬 研究方法

Referred in 主笔记