近日，美国马萨诸塞州总医院Thorsten R. Mempel研究发现，迁移性树突状细胞（DC）激活细胞因子转化生长因子β（TGF-β）来预处理初始CD8阳性T细胞，从而确立组织驻留记忆T细胞的命运。该研究于2019年10月11日发表在《科学》杂志上。
研究人员发现在免疫稳态期间，TGF-β在表观遗传学上调节了静息的初始CD8阳性T细胞，并为在皮肤疫苗接种小鼠模型中形成表皮常驻记忆T（eTRM）细胞做好准备。初始T细胞调节发生在淋巴结（LN）中，但不发生在脾脏中，这是通过与周围组织来源的迁移性DC的主要组织相容性复合物I（MHC I）依赖性相互作用而发生的，并且取决于TGF-β激活αV型整合素在DC的表达。因此，通过限制LN的信号，免疫前T细胞库能够为向特异性记忆T细胞分化命运做好准备。
据介绍，eTRM细胞是屏障组织中的前哨，以防御先前遇到的病原体。eTRM细胞的产生方式对通过免疫接种诱导自身形成或预防自身免疫性疾病具有重要意义。
附：英文原文
Title: Migratory DCs activate TGF-β to precondition naive CD8+ T cells for tissue-resident memory fate
Author: Vinidhra Mani, Shannon K. Bromley, Tarmo ij, Rut Mora-Buch, Esteban Carrizosa, Ross D. Warner, Moustafa Hamze, Debattama R. Sen, Alexandra Y. Chasse, Alina Lorant, Jason W. Griffith, Rod A. Rahimi, Craig P. McEntee, Kate L. Jeffrey, Francesco Marangoni, Mark A. Travis, Adam Lacy-Hulbert, Andrew D. Luster, Thorsten R. Mempel
Issue&Volume: Volume 366 Issue 6462
Abstract:
Epithelial resident memory T (eTRM) cells serve as sentinels in barrier tissues to guard against previously encountered pathogens. How eTRM cells are generated has important implications for efforts to elicit their formation through vaccination or prevent it in autoimmune disease. Here, we show that during immune homeostasis, the cytokine transforming growth factor β (TGF-β) epigenetically conditions resting naïve CD8+ T cells and prepares them for the formation of eTRM cells in a mouse model of skin vaccination. Naïve T cell conditioning occurs in lymph nodes (LNs), but not in the spleen, through major histocompatibility complex class I–dependent interactions with peripheral tissue–derived migratory dendritic cells (DCs) and depends on DC expression of TGF-β–activating αV integrins. Thus, the preimmune T cell repertoire is actively conditioned for a specialized memory differentiation fate through signals restricted to LNs.
DOI: 10.1126/science.aav5728
Source: https://science.sciencemag.org/content/366/6462/eaav5728