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Antigen Presentation by Human Microvascular Endothelial Cells Triggers ICAM-1-Dependent Transendothelial Protrusion by, and Fractalkine-Dependent Transendothelial Migration of, Effector Memory CD4⁺ T Cells¹

Thomas D. Manes^* and Jordan S. Pober^2,*,,

^* Department of Immunobiology, Department of Pathology, and Department of Dermatology, Yale University School of Medicine, New Haven, CT 06520

TCR engagement on adherent human effector memory CD4⁺ T cells by TNF-treated HUVECs under flow induces formation of a transendothelial protrusion (TEP) by the T cell but fails to induce transendothelial migration (TEM). In contrast, TCR engagement of the same T cell populations by TNF-treated human dermal microvascular cells (HDMEC) not only induces TEP formation, but triggers TEM at or near the interendothelial cell junctions via a process in which TEP formation appears to be the first step. Transduction of adhesion molecules in unactivated HDMEC and use of blocking Abs as conducted with TNF-activated HDMEC indicate that ICAM-1 plays a nonredundant role in TCR-driven TEP formation and TEM, and that TCR-driven TEM is also dependent upon fractalkine. TEP formation, dependence on ICAM-1, and dependence on fractalkine distinguish TCR-induced TEM from IP-10-induced TEM. These in vitro observations suggest that presentation of Ag by human microvascular endothelial cells to circulating CD4⁺ effector memory T cells may function to initiate recall responses in peripheral tissues.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by National Institute of Health Grants P01-HL070295 and HL051014.

² Address correspondence and reprint requests to Dr. Jordan S. Pober, Yale University School of Medicine, Amistad Research Building, Room 401, 10 Amistad Street, New Haven, CT 06520. E-mail address: jordan.pober{at}yale.edu

³ Abbreviations used in this paper: EC, endothelial cell; TEM, transendothelial migration; EM, effector memory; HDMEC, human dermal microvascular endothelial cell; TEP, transendothelial protrusion; DAPI, 4',6'-diamidino-2-phenylindole; TSST-1, toxic shock syndrome toxin-1; CM, central memory; IP, invasive podosome; PTX, pertussis toxin.

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