受体CD28和CTLA-4环路可调节T细胞群体动态
2020-02-13   阅读:417   来源:细胞

德国弗莱堡大学Jan C. Rohr课题组研究发现通过受体CD28和CTLA-4介导的嵌套拮抗反馈环路进行群体调控会赋予T细胞群体动态稳健性。相关论文2020年2月11日发表于国际学术期刊《免疫》上。

他们使用延时显微镜、遗传干扰、生物信息学预测和数学模型研究这个问题。他们发现ICAM-1介导的细胞群集使CD8 + T细胞能够共同调节增殖和凋亡之间的平衡。从机制上讲,T细胞表达的CD80和CD86与相邻T细胞上的受体CD28和CTLA-4相互作用。这些相互作用为两个嵌套的拮抗反馈回路提供了信号,该回路以依赖于T细胞密度的方式调节白介素2的产生,这已被该网络的体内调节证实。因此,CD8 + T细胞内在调节机制调节细胞行为,从而促进群体动态的稳健性。

据了解,感染后的T细胞反应表现出显著可复制扩张、收缩和记忆形成模式。是否这种模式的稳健性完全建立在源自其他细胞类型的信号或激活的T细胞本身是否参与了这些群体动态的编排(类似于细菌群体调控)尚不清楚。

附:英文原文

Title: Quorum Regulation via Nested Antagonistic Feedback Circuits Mediated by the Receptors CD28 and CTLA-4 Confers Robustness to T Cell Population Dynamics

Author: Simon Zenke, Margriet M. Palm, Julia Braun, Alina Gavrilov, Philippa Meiser, Jan P. Bttcher, Niklas Beyersdorf, Stephan Ehl, Audrey Gerard, Tim Lmmermann, Ton N. Schumacher, Joost B. Beltman, Jan C. Rohr

Issue&Volume: February 11, 2020

Abstract: T cell responses upon infection display a remarkably reproducible pattern of expansion,contraction, and memory formation. If the robustness of this pattern builds entirelyon signals derived from other cell types or if activated T cells themselves contributeto the orchestration of these population dynamics—akin to bacterial quorum regulation—isunclear. Here, we examined this question using time-lapse microscopy, genetic perturbation,bioinformatic predictions, and mathematical modeling. We found that ICAM-1-mediatedcell clustering enabled CD8+ T cells to collectively regulate the balance between proliferation and apoptosis.Mechanistically, T cell expressed CD80 and CD86 interacted with the receptors CD28and CTLA-4 on neighboring T cells; these interactions fed two nested antagonisticfeedback circuits that regulated interleukin 2 production in a manner dependent onT cell density as confirmed by in vivo modulation of this network. Thus, CD8+ T cell-population-intrinsic mechanisms regulate cellular behavior, thereby promotingrobustness of population dynamics.

DOI: 10.1016/j.immuni.2020.01.018

编辑:小柯机器人

©2020年04月06日 19:21:51
基因在线
0.0944s加载完成
北京艾迪灵科技有限公司 旗下网站