Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia
Vascular Immunology Unit, Discipline of Pathology, Sydney Medical School, University of Sydney, Camperdown, New South Wales 2050, Australia.
J Immunol. 2014 Oct 1;193(7):3378-87. doi: 10.4049/jimmunol.1303431. Epub 2014 Sep 3.
Endothelial cells closely interact with circulating lymphocytes. Aggression or activation of the endothelium leads to an increased shedding of endothelial cell microparticles (MP). Endothelial MP (EMP) are found in high plasma levels in numerous immunoinflammatory diseases, such as atherosclerosis, sepsis, multiple sclerosis, and cerebral malaria, supporting their role as effectors and markers of vascular dysfunction. Given our recently described role for human brain microvascular endothelial cells (HBEC) in modulating immune responses, we investigated how HBEC-derived MP could interact with and support the proliferation of T cells. Like their mother cells, EMP expressed molecules important for Ag presentation and T cell costimulation, that is, β2-microglobulin, MHC II, CD40, and ICOSL. HBEC were able to take up fluorescently labeled Ags with EMP also containing fluorescent Ags, suggestive of Ag carryover from HBEC to EMP. In cocultures, fluorescently labeled EMP from resting or cytokine-stimulated HBEC formed conjugates with both CD4(+) and CD8(+) subsets, with higher proportions of T cells binding EMP from cytokine-stimulated cells. The increased binding of EMP from cytokinestimulated HBEC to T cells was VCAM-1 and ICAM-1 dependent. Finally, in CFSE T cell proliferation assays using anti-CD3 mAb or T cell mitogens, EMP promoted the proliferation of CD4(+) T cells and that of CD8(+) T cells in the absence of exogenous stimuli and in the T cell mitogenic stimulation. Our findings provide novel evidence that EMP can enhance T cell activation and potentially ensuing Ag presentation, thereby pointing toward a novel role for MP in neuroimmunological complications of infectious diseases.
内皮细胞与循环淋巴细胞密切相互作用。内皮细胞的侵袭或激活导致内皮细胞微颗粒（MP）的脱落增加。内皮 MP（EMP）在许多免疫炎症性疾病中，如动脉粥样硬化、败血症、多发性硬化症和脑疟疾，其血浆水平升高，支持其作为血管功能障碍的效应物和标志物的作用。鉴于我们最近描述的人脑血管内皮细胞（HBEC）在调节免疫反应中的作用，我们研究了 HBEC 衍生的 MP 如何与 T 细胞相互作用并支持其增殖。与母细胞一样，EMP 表达了与抗原呈递和 T 细胞共刺激有关的重要分子，即β2-微球蛋白、MHC II、CD40 和 ICOSL。HBEC 能够摄取带有 EMP 的荧光标记的 Ag，而 EMP 也含有荧光 Ag，提示 Ag 从 HBEC 转移到 EMP。在共培养物中，静息或细胞因子刺激的 HBEC 的荧光标记 EMP 与 CD4(+)和 CD8(+)亚群形成了共轭，来自细胞因子刺激细胞的 EMP 与更多比例的 T 细胞结合。细胞因子刺激的 HBEC 的 EMP 与 T 细胞的结合增加依赖于 VCAM-1 和 ICAM-1。最后，在使用抗 CD3 mAb 或 T 细胞有丝分裂原的 CFSE T 细胞增殖测定中，EMP 促进了 CD4(+)T 细胞和 CD8(+)T 细胞的增殖，而无需外源性刺激和 T 细胞有丝分裂原刺激。我们的研究结果提供了新的证据，表明 EMP 可以增强 T 细胞的激活，并可能随之进行抗原呈递，从而为 MP 在感染性疾病的神经免疫并发症中的新作用提供了线索。
