Objective-CD155 is a cell surface protein that has recently been described to exert immune regulatory functions. We have characterized the expression of CD155 on human vascular endothelial cells (ECs) and examined its role in the regulation of T-cell activation. Methods and Results-CD155 was expressed on resting human vascular ECs and was upregulated in an interferon-␥ (IFN␥)-dependent manner. When the function of CD155 in regulating T-cell activation was examined, antibodymediated neutralization of CD155 did not affect CD8 T-cell proliferation in response to stimulation with ECs. However, neutralization of CD155 activity or small interfering RNA-mediated inhibition of CD155 expression in ECs increased expression of IFN␥ and cytotoxic effector function in activated CD8 T cells. Key Words: cytokines Ⅲ endothelium Ⅲ immune system Ⅲ CD155 Ⅲ T cell H uman vascular endothelial cells (ECs) act as semiprofessional antigen-presenting cells and, in this way, regulate immune responses by presenting antigenic peptides and cell surface proteins to T cells in peripheral tissues. 1,2 This immunoregulatory property of the endothelium is established in the control T-cell responses in solid organ transplantation and may regulate immune responses in autoimmunity and some cardiovascular diseases. 1 With regard to the expression of cell surface proteins, human ECs provide positive costimulatory signals to T cells mainly through leukocyte functional antigen-3, intercellular adhesion molecule-1, CD154, 41BB ligand, inducible co-stimulator ligand, and OX40 ligand. 3 These signals are required for the activation of memory CD4 and CD8 T cells by ECs. In contrast, ECs also express cell surface proteins, such as PD-L1, that inhibit T cell responses. 4,5 The expression of immune regulatory proteins on ECs is controlled by cytokines. In particular, interferon-␥ (IFN␥) is especially pertinent to EC immunobiology as it induces the expression of both immune activating and inhibitory proteins. 6,7 The precise effects of IFN␥ on determining the phenotype of ECs may depend on its cooperative signaling with other cytokines or the temporal regulation of target genes. Overall, understanding the role of immune regulatory proteins on the surface of ECs is important for providing insight into the regulation of immune responses.
Conclusion-CD155Activation of CD8 T cells by allogeneic human ECs induces proliferation, IFN␥ secretion, and the expression of cytotoxic effector proteins, such as granzyme B. 8 These properties of activated CD8 T cells play a pathological role in allograft rejection. 9 Also, IFN␥ production from activated T cells within arteries drives pathological smooth muscle cell proliferation in the arterial intima and vasomotor dysfunction, thereby contributing to the pathogenesis of some vascular diseases. 10 Interleukin (IL)-10 is also produced by effector T cells that secrete IFN␥, as well as by some induced regulatory T cells. Expression of IL-10 in effector T cells develops late after T-cell activation, correlates with increased i...