Carman Christopher V, Martinelli Roberta
Center for Vascular Biology Research, Department of Medicine and Emergency Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School , Boston, MA , USA.
Front Immunol. 2015 Nov 24;6:603. doi: 10.3389/fimmu.2015.00603. eCollection 2015.
Antigen-specific immunity requires regulated trafficking of T cells in and out of diverse tissues in order to orchestrate lymphocyte development, immune surveillance, responses, and memory. The endothelium serves as a unique barrier, as well as a sentinel, between the blood and the tissues, and as such it plays an essential locally tuned role in regulating T cell migration and information exchange. While it is well established that chemoattractants and adhesion molecules are major determinants of T cell trafficking, emerging studies have now enumerated a large number of molecular players as well as a range of discrete cellular remodeling activities (e.g., transmigratory cups and invadosome-like protrusions) that participate in directed migration and pathfinding by T cells. In addition to providing trafficking cues, intimate cell-cell interaction between lymphocytes and endothelial cells provide instruction to T cells that influence their activation and differentiation states. Perhaps the most intriguing and underappreciated of these "sentinel" roles is the ability of the endothelium to act as a non-hematopoietic "semiprofessional" antigen-presenting cell. Close contacts between circulating T cells and antigen-presenting endothelium may play unique non-redundant roles in shaping adaptive immune responses within the periphery. A better understanding of the mechanisms directing T cell trafficking and the antigen-presenting role of the endothelium may not only increase our knowledge of the adaptive immune response but also empower the utility of emerging immunomodulatory therapeutics.
抗原特异性免疫需要T细胞在不同组织中进行有调控的出入运输，以协调淋巴细胞的发育、免疫监视、免疫反应和免疫记忆。内皮细胞在血液和组织之间充当独特的屏障以及哨兵，因此在调节T细胞迁移和信息交换方面发挥着至关重要的局部调节作用。虽然趋化因子和黏附分子是T细胞运输的主要决定因素这一点已得到充分证实，但新出现的研究现已列举出大量分子参与者以及一系列离散的细胞重塑活动（例如迁移杯和侵袭样突起），这些都参与了T细胞的定向迁移和路径寻找。除了提供运输线索外，淋巴细胞和内皮细胞之间密切的细胞间相互作用还为T细胞提供指令，影响其激活和分化状态。内皮细胞作为非造血“半专业”抗原呈递细胞的能力，可能是这些“哨兵”作用中最引人入胜且未得到充分重视的。循环T细胞与抗原呈递内皮细胞之间的紧密接触，可能在塑造外周适应性免疫反应中发挥独特的非冗余作用。更好地理解指导T细胞运输的机制以及内皮细胞的抗原呈递作用，不仅可能增加我们对适应性免疫反应的了解，还可能增强新兴免疫调节疗法的效用。
