瑞士巴塞尔大学Christoph Hess研究小组发现，LFA-1介导的镁离子感应调控CD8⁺ T细胞的效应子功能。相关论文于2022年1月19日在线发表于国际学术期刊《细胞》。

研究人员发现，共刺激细胞表面分子LFA-1需要镁离子来实现其在CD8⁺ T细胞上的活性构象，从而增强钙流量、信号转导、代谢重编程、免疫突触的形成，以及作为结果的特定细胞毒性。因此，通过LFA-1感知的镁离子充足能够转化为病原体和肿瘤特异性T细胞的卓越表现，增强了双特异性T细胞结合抗体的有效性，并改善了CAR T细胞的功能。

在临床上CAR T细胞和免疫检查点抗体治疗的患者中，低血清镁离子水平与更快的疾病进展和更短的总生存期有关。因此，LFA-1直接整合了关于微环境组成的信息来作为外向型信号活动的决定因素。这些发现在概念上将共刺激和营养感应联系起来，并指出镁离子-LFA-1轴是一个可治疗操控的生物系统。

据悉，细胞外镁离子在细胞免疫中的相关性在很大程度上仍然是未知的。

附：英文原文

Title: Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Author: Jonas Ltscher, Adrià-Arnau Martí i Líndez, Nicole Kirchhammer, Elisabetta Cribioli, Greta Giordano, Marcel P. Trefny, Markus Lenz, Sacha I. Rothschild, Paolo Strati, Marco Künzli, Claudia Lotter, Susanne H. Schenk, Philippe Dehio, Jordan Lliger, Ludivine Litzler, David Schreiner, Victoria Koch, Nicolas Page, Dahye Lee, Jasmin Grhlert, Dmitry Kuzmin, Anne-Valérie Burgener, Doron Merkler, Miklos Pless, Maria L. Balmer, Walter Reith, Jrg Huwyler, Melita Irving, Carolyn G. King, Alfred Zippelius, Christoph Hess

Issue&Volume: 2022-01-19

Abstract: The relevance of extracellular magnesium in cellular immunity remains largely unknown.Here, we show that the co-stimulatory cell-surface molecule LFA-1 requires magnesiumto adopt its active conformation on CD8+ T cells, thereby augmenting calcium flux, signal transduction, metabolic reprogramming,immune synapse formation, and, as a consequence, specific cytotoxicity. Accordingly,magnesium-sufficiency sensed via LFA-1 translated to the superior performance of pathogen-and tumor-specific T cells, enhanced effectiveness of bi-specific T cell engagingantibodies, and improved CAR T cell function. Clinically, low serum magnesium levelswere associated with more rapid disease progression and shorter overall survival inCAR T cell and immune checkpoint antibody-treated patients. LFA-1 thus directly incorporatesinformation on the composition of the microenvironment as a determinant of outside-insignaling activity. These findings conceptually link co-stimulation and nutrient sensingand point to the magnesium-LFA-1 axis as a therapeutically amenable biologic system.

DOI: 10.1016/j.cell.2021.12.039

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)01561-0