Institute of Immunology and Immunotherapy, University of Birmingham Birmingham, United Kingdom.
NHS Blood and Transplant, Birmingham, United Kingdom.
Front Immunol. 2019 Mar 15;10:468. doi: 10.3389/fimmu.2019.00468. eCollection 2019.
CD117 (cKit) is the receptor for stem cell factor (SCF) and plays an important role in early haemopoiesis. We show that CD117 is also expressed following priming of mature human CD8 T cells and is detectable following primary infection . CD117 expression is mediated through an intrinsic pathway and is suppressed by IL-12. Importantly, the extent of CD117 expression is inversely related to the strength of the activating stimulus and subsequent engagement with cell-bound SCF markedly increases susceptibility to apoptosis. CD117 is therefore likely to shape the pattern of CD8 T cell immunodominance during a primary immune response by rendering cells with low avidity for antigen more prone to apoptosis. Furthermore, CD117 T cells are highly sensitive to apoptosis mediated by galectin-1, a molecule commonly expressed within the tumor microenvironment, and CD117 expression may therefore represent a novel and potentially targetable mechanism of tumor immune evasion.
CD117(cKit)是干细胞因子(SCF)的受体,在早期造血中发挥重要作用。我们表明,在成熟的人 CD8 T 细胞的初始激活后也表达 CD117 ,并且可以在初次感染后检测到。CD117 的表达是通过内在途径介导的,并受 IL-12 抑制。重要的是,CD117 的表达程度与激活刺激的强度呈负相关,并且与细胞结合的 SCF 的结合明显增加了对细胞凋亡的易感性。因此,CD117 可能通过使对抗原低亲和力的细胞更容易凋亡,从而在初次免疫反应中塑造 CD8 T 细胞免疫优势的模式。此外,CD117 T 细胞对 galectin-1 介导的凋亡高度敏感,galectin-1 是肿瘤微环境中常见表达的分子,因此 CD117 的表达可能代表肿瘤免疫逃逸的一种新的潜在靶向机制。