Endothelial Cells Augment the Suppressive Function of CD4+ CD25+Foxp3+ Regulatory T Cells: Involvement of Programmed Death-1 and IL-10

Blood endothelial cells (ECs) act as gatekeepers to coordinate the extravasation of different T cell subpopulations. ECs express defined panels of adhesion molecules, facilitating interaction with blood circulating T cells. In addition to the mere adhesion, this cellular interaction between ECs and transmigrating I cells may also provide signals that affect the phenotype and function of the T cells. To test the effects of ECs on regulatory T cells (T-reg) we set up cocultures of freshly isolated murine T-reg and primary ECs and assessed the phenotype and function of the T-reg. We show that T-reg upregulate programmed death-1 (PD-1) receptor expression, as well IL-10 and TGF-beta secretion after contact to ECs. These changes in phenotype were accompanied by an increased suppressive capacity of the T-reg. Blockade of the PD-1 and/or the IL-10 secretion in the in vitro suppression assays abrogated the enhanced suppressive capacity, indicating relevance of these molecules for the enhanced suppressive activity of T-reg. In aggregate, our data show, that ECs increase the immunosuppressive potential of activated T-reg by upregulation of PD-1 and stimulation of the production of high levels of IL-10 and TGF-beta. Therefore, one can speculate that T-reg during transendothelial transmigration become "armed" for their suppressive function(s) to be carried out in peripheral tissues sites. The Journal of Immunology, 2010, 184: 5562-5570.