CD279通过增强T细胞与巨噬细胞的相互作用来介导调节性T细胞的稳态和存活。,FEBS Open Bio

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CD279通过增强T细胞与巨噬细胞的相互作用来介导调节性T细胞的稳态和存活。
FEBS Open Bio ( IF 2.8 ) Pub Date : 2020-05-13 , DOI: 10.1002/2211-5463.12865
Yang Liu ₁ , Yuting Gao ₁ , Huiqin Hao ₁ , Tiezheng Hou ₁

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CD279是主要在T细胞上表达的细胞表面蛋白。它的配体CD273和CD274在抗原呈递细胞和肿瘤上表达。已证明CD279可通过抑制CD8 T细胞活化而充当重要的免疫检查点，而针对CD279的抗体可增强T细胞介导的细胞毒性功能。然而，CD279是否在CD4 T细胞稳态或介导T细胞与抗原呈递细胞的相互作用中具有其他功能仍不清楚。在本研究中，我们表明抗体介导的对CD279的抑制作用会降低体内T细胞的存活率。出乎意料的是，CD279阻断还通过减少它们的接触时间而损害了调节性T细胞和巨噬细胞的相互作用。CD273拮抗剂几乎没有作用的观察结果表明，CD274（CD279的第二个配体）在常规T细胞（Tcon）和巨噬细胞之间的接触中起着更重要的作用。本研究的结果表明，两种CD279配体都有助于T细胞与巨噬细胞之间的相互作用，这是维持Treg稳态的机制。此外，CD273和CD274并不是多余的配体，因为CD274在这个复杂的免疫轴上可能对Tcon具有独特的作用。因此，选择作为癌症免疫治疗工具的检查点阻断配体对于抗肿瘤T细胞活化和避免副作用具有重要意义。

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CD279 mediates the homeostasis and survival of regulatory T cells by enhancing T cell and macrophage interactions.

CD279 is a cell surface protein predominantly expressed on T cells. Its ligands CD273 and CD274 are expressed on antigen‐presenting cells and tumors. CD279 has been shown to act as an important immune check point by inhibiting CD8 T cell activation, and antibodies against CD279 enhance T cell‐mediated cytotoxic function. However, whether CD279 has other functions in CD4 T cell homeostasis or in mediating T cell interactions with antigen‐presenting cells remains unclear. In the present study, we show that antibody‐mediated inhibition of CD279 reduces T cell survival in bone marrow in vivo. Unexpectedly, CD279 blockade also compromised regulatory T cell and macrophage interactions by reducing their contact time. The observation that the CD273 antagonist had little effect suggests that CD274 (the second ligand of CD279) plays a more central role in contact between conventional T cells (Tcon) and macrophages. The results of the present study suggest that both CD279 ligands contribute to the interaction length between T cells and macrophages as a mechanism of maintaining Treg homeostasis. Furthermore, CD273 and CD274 are not redundant ligands because CD274 may have unique effects on Tcon in this complex immune axis. Therefore, ligand selection for check point blockade as a tool for cancer immunotherapy has important implications with respect to anti‐tumor T cell activation and the avoidance of side effects.

更新日期：2020-05-13

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