CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities
CD4+ T cell help creates memory CD8+ T cells with innate and help-independent recall capacities
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DOI：
10.1038/s41467-019-13438-1
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发表时间：
2019-12-04
影响因子：
16.6
通讯作者：
Borst, Jannie
中科院分区：
文献类型：
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作者：
Ahrends, Tomasz;Busselaar, Julia;Borst, Jannie
CD 8（+）细胞毒性T淋巴细胞（CTL）记忆的产生需要CD 4（+）T细胞的帮助。在这里，我们使用全基因组分析，以显示如何CD 4（+）T细胞帮助在启动过程中提供促进CTL的记忆分化。辅助信号增强IL-15依赖性维持中央记忆T（T-CM）细胞。更重要的是，帮助信号调节效应记忆T（T-EM）细胞池的大小和功能。在IL-12和IL-18的抗原非依赖性先天样回忆后，帮助T-EM细胞产生颗粒酶B和IFN γ。此外，帮助记忆CTL表达效应程序特性的帮助初级CTL回忆与MHC I类限制性抗原，可能是由于表观遗传印记和持续的mRNA表达效应基因。因此，我们的数据表明，在启动过程中，CD 4（+）T细胞通过产生具有先天性和辅助非依赖性抗原特异性回忆能力的T-EM细胞来帮助优化CTL记忆。
CD4(+) T cell help is required for the generation of CD8(+) cytotoxic T lymphocyte (CTL) memory. Here, we use genome-wide analyses to show how CD4(+) T cell help delivered during priming promotes memory differentiation of CTLs. Help signals enhance IL-15-dependent maintenance of central memory T (T-CM) cells. More importantly, help signals regulate the size and function of the effector memory T (T-EM ) cell pool. Helped T-EM cells produce Granzyme B and IFN gamma upon antigen-independent, innate-like recall by IL-12 and IL-18. In addition, helped memory CTLs express the effector program characteristic of helped primary CTLs upon recall with MHC class I-restricted antigens, likely due to epigenetic imprinting and sustained mRNA expression of effector genes. Our data thus indicate that during priming, CD4(+) T cell help optimizes CTL memory by creating T-EM cells with innate and helpindependent antigen-specific recall capacities.