Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine Charlottesville, VA, USA ; Carter Immunology Center, University of Virginia School of Medicine Charlottesville, VA, USA.
Front Immunol. 2012 Sep 28;3:305. doi: 10.3389/fimmu.2012.00305. eCollection 2012.
The lymphatic vasculature provides routes for dendritic cell and lymphocyte migration into and out of lymph nodes. Lymphatic endothelial cells (LEC) control these processes by expression of CCL21, sphingosine-1-phosphate, and adhesion molecules. LEC express MHC-I and MHC-II, but not costimulatory molecules, and present antigen on MHC-I via both direct and cross-presentation. Whether LEC present to CD4 T cells on MHC-II is unknown. Interestingly, LEC express antigens otherwise restricted to a small number of peripheral tissues in an autoimmune regulatory element-independent manner. Direct presentation of peripheral tissue antigens (PTA) to CD8 T cells results in abortive proliferation and deletion, due to both a lack of costimulation and active PD-L1 engagement. Autoimmunity develops when deletion is subverted, suggesting that LEC presentation of PTA could lead to human disease if PD-1 signaling were impaired by genetic polymorphisms, or aberrant costimulation occurred during inflammation. The expression of additional inhibitory molecules, which are not involved in LEC-mediated deletion, suggests that LEC may have additional immunoregulatory roles. LEC express receptors for several immunomodulatory molecules whose engagement alters their phenotype and function. In this review we describe the role of LEC in distinct anatomical locations in controlling immune cell trafficking, as well as their emerging role in the regulation of T cell tolerance and immunity.
淋巴管为树突状细胞和淋巴细胞进出淋巴结提供了途径。淋巴内皮细胞（LEC）通过表达 CCL21、鞘氨醇-1-磷酸和黏附分子来控制这些过程。LEC 表达 MHC-I 和 MHC-II，但不表达共刺激分子，并通过直接和交叉呈递在 MHC-I 上呈递抗原。LEC 是否在 MHC-II 上呈递抗原给 CD4 T 细胞尚不清楚。有趣的是，LEC 以一种自身免疫调节元件独立的方式表达通常局限于少数外周组织的抗原。外周组织抗原（PTA）的直接呈递导致 CD8 T 细胞的无效增殖和删除，这是由于缺乏共刺激和 PD-L1 的主动结合。当删除被颠覆时，自身免疫就会发展，这表明如果 PD-1 信号因遗传多态性受损，或者在炎症过程中发生异常共刺激，LEC 呈递 PTA 可能导致人类疾病。表达其他不参与 LEC 介导的删除的抑制性分子表明，LEC 可能具有额外的免疫调节作用。LEC 表达几种免疫调节分子的受体，其结合改变了它们的表型和功能。在这篇综述中，我们描述了 LEC 在控制免疫细胞迁移的不同解剖位置中的作用，以及它们在调节 T 细胞耐受和免疫方面的新兴作用。
