CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis.
CD80 on Human T Cells Is Associated With FoxP3 Expression and Supports Treg Homeostasis.
复制标题
DOI：
10.3389/fimmu.2020.577655
复制
发表时间：
2020
影响因子：
7.3
通讯作者：
Sansom DM
中科院分区：
文献类型：
--
作者：
Soskic B;Jeffery LE;Kennedy A;Gardner DH;Hou TZ;Halliday N;Williams C;Janman D;Rowshanravan B;Hirschfield GM;Sansom DM
CD80和CD86在抗原呈递细胞（APCs）上表达，它们在T细胞共刺激中的作用已得到证实。然而，已经证明这些分子也可以被T细胞表达，但这一观察的意义尚不清楚。我们研究了控制CD80和CD86在T细胞上表达的刺激，并表明在无apc的条件下，大约40%的活化、增殖的CD4+ T细胞表达CD80、CD86或两者兼有。CD80和CD86的表达强烈依赖于提供CD28共刺激，因为单独刺激TCR后配体不表达。此外，我们观察到CD80+ T细胞具有诱导调节性T细胞（iTreg）的特征，表达Foxp3和高水平的CTLA-4，但增殖较少。相比之下，CD86优先表达在产生INF-γ的细胞上，这些细胞增殖更广泛，具有效应T细胞的特征。最后，我们证明了在T细胞上表达的CD80抑制CTLA-4功能，促进iTreg的生长。综上所述，这些数据确定了活化T细胞内源性CD80和CD86的表达不是由于配体被转内吞作用捕获，并突出了它们的表达模式和相关功能的明显差异。
CD80 and CD86 are expressed on antigen presenting cells (APCs) and their role in providing costimulation to T cells is well established. However, it has been shown that these molecules can also be expressed by T cells, but the significance of this observation remains unknown. We have investigated stimuli that control CD80 and CD86 expression on T cells and show that in APC-free conditions around 40% of activated, proliferating CD4+ T cells express either CD80, CD86 or both. Expression of CD80 and CD86 was strongly dependent upon provision of CD28 costimulation as ligands were not expressed following TCR stimulation alone. Furthermore, we observed that CD80+ T cells possessed the hallmarks of induced regulatory T cells (iTreg), expressing Foxp3 and high levels of CTLA-4 whilst proliferating less extensively. In contrast, CD86 was preferentially expressed on INF-γ producing cells, which proliferated more extensively and had characteristics of effector T cells. Finally, we demonstrated that CD80 expressed on T cells inhibits CTLA-4 function and facilitates the growth of iTreg. Together these data establish endogenous expression of CD80 and CD86 by activated T cells is not due to ligand capture by transendocytosis and highlight clear differences in their expression patterns and associated functions.