Vora M, Yssel H, de Vries J E, Karasek M A
Department of Dermatology, Stanford University School of Medicine, CA 94305-5486.
J Immunol. 1994 Jun 15;152(12):5734-41.
Human dermal microvascular endothelial cells (HDMEC) play a central role in many aspects of the inflammatory and immune reactions in skin. HDMEC display a phenotypic diversity ranging from cells with an epithelioid morphology to those that show both morphologic and biochemical characteristics of macrophages. Here it is shown that HDMEC possess the capability to both process and present Ags. T lymphocyte clones specific for peptide p94-104, which are derived from the protein of group I allergen of Dermatophagoides pteronyssinus, a major house dust mite allergen, and restricted by HLADR11, proliferated specifically to stimulation with the group I allergen of D. pteronyssinus and with peptide p94-104 presented by HDMEC. Preincubation for 48 h with IFN-gamma enhanced the expression of class II MHC Ags on HDMEC, which in turn increased the capacity of HDMEC to present Ag. When HDMEC were primed with Ag in the presence of IL-10, a 75% inhibition of Ag-specific T cell proliferation was observed. IL-10 also inhibited T cell proliferation induced by IFN-gamma-stimulated HDMEC. These findings demonstrate that HDMEC possess the ability to process and present Ag to CD4+ T cells and that these reactions are stimulated by IFN-gamma and inhibited by IL-10. The reduced Ag-presenting capacity of HDMEC mediated by IL-10 is not associated with a down-regulation of class II MHC expression. No significant reduction of HLA-DR expression was detected either at the protein or gene level when HDMEC were incubated with IFN-gamma and IL-10 as compared with incubation with IFN-gamma alone. The profound down-regulatory effect of IL-10 on Ag presentation may provide a new pharmacologic approach to control inflammatory responses in skin.
人真皮微血管内皮细胞（HDMEC）在皮肤炎症和免疫反应的许多方面发挥着核心作用。HDMEC表现出表型多样性，从具有上皮样形态的细胞到那些兼具巨噬细胞形态学和生化特征的细胞。本文表明HDMEC具有处理和呈递抗原的能力。源自主要屋尘螨过敏原——粉尘螨I组变应原蛋白、受HLA - DR11限制的针对肽p94 - 104的T淋巴细胞克隆，对粉尘螨I组变应原以及HDMEC呈递的肽p94 - 104刺激有特异性增殖反应。用γ干扰素预孵育48小时可增强HDMEC上II类MHC抗原的表达，这反过来又增加了HDMEC呈递抗原的能力。当HDMEC在白细胞介素 - 10存在下用抗原致敏时，观察到抗原特异性T细胞增殖受到75%的抑制。白细胞介素 - 10还抑制由γ干扰素刺激的HDMEC诱导的T细胞增殖。这些发现表明HDMEC具有处理抗原并将其呈递给CD4 + T细胞的能力，并且这些反应受到γ干扰素的刺激和白细胞介素 - 10的抑制。白细胞介素 - 10介导的HDMEC抗原呈递能力降低与II类MHC表达下调无关。与仅用γ干扰素孵育相比，当HDMEC与γ干扰素和白细胞介素 - 10一起孵育时，在蛋白质或基因水平均未检测到HLA - DR表达的显著降低。白细胞介素 - 10对抗原呈递的深刻下调作用可能为控制皮肤炎症反应提供一种新的药理学方法。
