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效应体 CD8 T 细胞分化为长寿命记忆细胞
Ben Youngblood1,2,3, J Scott Hale1,2, Haydn T Kissick4
1Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
Nature
|December 14, 2017
概括
长寿记忆CD8T细胞通过脱差过程从效应T细胞的子集发展. 这涉及到表观遗传重编程,其中天真细胞基因被重新表达,使得T细胞免疫力强大.
科学领域:
- 免疫学
- 细胞生物学
- 表观遗传学
背景情况:
- 长期存储的CD8T细胞对于适应性免疫至关重要,在病原体再次暴露时提供快速反应.
- 记忆 CD8 T 细胞的发育起源,无论是来自原始细胞还是效应细胞,一直存在着长期的争论.
- 记忆CD8T细胞表现出原始和效应细胞的特征,使其谱系的确定变得复杂.
研究的目的:
- 研究长寿记忆CD8T细胞的发育起源.
- 阐明控制从效应细胞向记忆CD8T细胞的表观遗传机制.
- 确定存储CD8T细胞是否直接来自原始细胞或通过从效应细胞的脱差过程产生.
主要方法:
- 在小鼠急性淋巴细胞胆炎病毒感染期间对病毒特异性CD8T细胞的DNA甲基化模式的分析.
- 终端效应体和记忆前体CD8 T细胞子集之间的表观遗传状态的比较.
- 条件删除新甲基转移酶Dnmt3a以评估其在记忆细胞发育中的作用.
- 传输的记忆前体效应细胞的长度表型和表观遗传特征.
主要成果:
- 记忆 CD8 T 细胞是通过脱差异化从效应 T 细胞的子集衍生而来的,而不是直接从原始细胞衍生而来的.
- 记忆细胞的发育涉及到在原始关联基因上获得新型DNA甲基化和在效应分子位点进行脱甲基化.
- 通过减少甲基化和促进原始基因的重新表达,Dnmt3a的条件删除加速了记忆细胞的发育.
- 对记忆细胞的分化与新甲基化和原始相关基因的重新表达的擦除有关.
结论:
- 长期存储的CD8T细胞来源于经历脱差的命运容许效应型T细胞的子集.
- 表观遗传重编程,特别是对原始相关基因表观遗传抑制的逆转,是记忆CD8T细胞形成的关键.
- 这项研究表明,记忆CD8T细胞通过涉及表观遗传可塑性的过程从效应细胞产生.
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