Carman, ChristopherMartinelli, Roberta2016-01-042015Carman, Christopher V., and Roberta Martinelli. 2015. “T Lymphocyte–Endothelial Interactions: Emerging Understanding of Trafficking and Antigen-Specific Immunity.” Frontiers in Immunology 6 (1): 603. doi:10.3389/fimmu.2015.00603. http://dx.doi.org/10.3389/fimmu.2015.00603.1664-3224http://nrs.harvard.edu/urn-3:HUL.InstRepos:23993460Antigen-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.en-USReviewlymphocyteTCRTraffickingendotheliumantigen presentationMHCimmunomodulationtoleranceJournal Article2016-01-0410.3389/fimmu.2015.00603