Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Vic., Australia.
Department of Medical Biology, University of Melbourne, Parkville, Vic., Australia.
Immunol Rev. 2021 Mar;300(1):203-219. doi: 10.1111/imr.12945. Epub 2021 Feb 14.
The relationship between the extrinsic environment and the internal transcriptional network is circular. Naive T cells first engage with antigen-presenting cells to set transcriptional differentiation networks in motion. In turn, this regulates specific chemokine receptors that direct migration into distinct lymph node niches. Movement into these regions brings newly activated T cells into contact with accessory cells and cytokines that reinforce the differentiation programming to specify T cell function. We and others have observed similarities in the transcriptional networks that specify both CD4+ T follicular helper (T ) cells and CD8+ central memory stem-like (T ) cells. Here, we compare and contrast the current knowledge for these shared differentiation programs, compared to their effector counterparts, CD4+ T-helper 1 (T ) and CD8+ short-lived effector (T ) cells. Understanding the interplay between cellular interactions and transcriptional programming is essential to harness T cell differentiation that is fit for purpose; to stimulate potent T cell effector function for the elimination of chronic infection and cancer; or to amplify the formation of humoral immunity and longevity of cellular memory to prevent infectious diseases.
外环境与内部转录网络之间的关系是循环的。初始 T 细胞首先与抗原呈递细胞相互作用，从而启动转录分化网络。反过来，这又调节了特定的趋化因子受体，使其定向迁移到不同的淋巴结龛位。进入这些区域后，新激活的 T 细胞与辅助细胞和细胞因子接触，这些细胞因子加强了分化程序，以指定 T 细胞的功能。我们和其他人观察到，在决定 CD4+滤泡辅助性 T（Tfh）细胞和 CD8+中央记忆干细胞样（Tcm）细胞的转录网络中存在相似性。在这里，我们将这些共同的分化程序与它们的效应物对应物 CD4+T 辅助 1（Tth1）和 CD8+短寿命效应（Ttex）细胞进行了比较和对比。了解细胞相互作用和转录编程之间的相互作用对于利用适合特定目的的 T 细胞分化、刺激强大的 T 细胞效应功能以消除慢性感染和癌症、或增强体液免疫的形成和细胞记忆的持久性以预防传染病至关重要。
