美国埃默里大学Mandy L. Ford团队近日取得一项新成果。他们的最新研究发现，通过抑制性Fc受体FcγRIIB发出的信号可诱导CD8⁺T细胞凋亡来限制T细胞免疫。2020年1月14日，国际知名学术期刊《免疫》发表了这一成果。

研究人员确定了活化和多轮分裂后表达抑制性Fc受体FcγRIIB的CD8⁺效应T细胞的亚群。Fcgr2b的CD8⁺T细胞内在遗传缺失会增加CD8⁺效应T细胞的积累，从而导致小鼠模型中移植物排斥反应加快和肿瘤体积减小。FcγRIIB介导的CD8⁺T细胞免疫控制不需要免疫球蛋白G（IgG）抗体，而是免疫抑制性细胞因子纤维蛋白原样2（Fgl2）作为CD8⁺T细胞上FcγRIIB的功能性配体。Fgl2诱导caspase-3/7介导的Fcgr2b⁺细胞凋亡，但不诱导Fcgr2b^-/-CD8⁺T细胞凋亡。在肾移植受者的临床试验中，FcγRIIB的表达增加与免疫抑制退出后排斥反应的解除相关。总之，这些发现证明了FcγRIIB在调节CD8⁺T细胞免疫力方面的细胞内在共抑制功能。

据介绍，CD8⁺效应T细胞是适应性免疫的重要介体，调节其存活的受体-配体相互作用可能具有治疗潜力。

附：英文原文

Title: Signaling through the Inhibitory Fc Receptor FcγRIIB Induces CD8+ T Cell Apoptosis to Limit T Cell Immunity

Author: Anna B. Morris, Clara R. Farley, David F. Pinelli, Layne E. Adams, Mark S. Cragg, Jeremy M. Boss, Christopher D. Scharer, Miguel Fribourg, Paolo Cravedi, Peter S. Heeger, Mandy L. Ford

Issue&Volume: 2020/01/14

Abstract: Effector CD8+ T cells are important mediators of adaptive immunity, and receptor-ligand interactionsthat regulate their survival may have therapeutic potential. Here, we identified asubset of effector CD8+ T cells that expressed the inhibitory fragment crystallizable (Fc) receptor FcγRIIBfollowing activation and multiple rounds of division. CD8+ T cell-intrinsic genetic deletion of Fcgr2b increased CD8+ effector T cell accumulation, resulting in accelerated graft rejection and decreasedtumor volume in mouse models. Immunoglobulin G (IgG) antibody was not required forFcγRIIB-mediated control of CD8+ T cell immunity, and instead, the immunosuppressive cytokine fibrinogen-like 2 (Fgl2)was a functional ligand for FcγRIIB on CD8+ T cells. Fgl2 induced caspase-3/7-mediated apoptosis in Fcgr2b+, but not Fcgr2b/, CD8+ T cells. Increased expression of FcγRIIB correlated with freedom from rejection followingwithdrawal from immunosuppression in a clinical trial of kidney transplant recipients.Together, these findings demonstrate a cell-intrinsic coinhibitory function of FcγRIIBin regulating CD8+ T cell immunity.

DOI: 10.1016/j.immuni.2019.12.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30525-4