Human endothelial cells generate Th17 and regulatory T cells under inflammatory conditions

Abstract

Organ transplantation represents a unique therapeutic option for irreparable organ dysfunction and rejection of transplants results from a breakdown in operational tolerance. Although endothelial cells (ECs) are the first target in graft rejection following kidney transplantation, their capacity to alloactivate and generate particular T lymphocyte subsets that could intervene in this process remains unknown. By using an experimental model of microvascular endothelium, we demonstrate that, under inflammatory conditions, human ECs induced proliferation of memory CD4 + CD45RA −

Seoul Virus-Infected Rat Lung Endothelial Cells and Alveolar Macrophages Differ in Their Ability To Support Virus Replication and Induce Regulatory T Cell Phenotypes

“…Treg cell induction by endothelial cells is PD-L1 dependent (41,72). SEOV infection of LMVECs increased PD-L1 protein expression.…”

“…Allogeneic T cell cocultures have been used previously to systematically evaluate APC induction of T cell responses during virus infection (55,56,76). This mixed lymphocyte reaction or allogeneic T cell coculture system also has been used to study the induction of Treg cells by activated murine vascular endothelial cells (41) and human endothelial cells (72). The allogeneic coculture system enabled identification of SEOV-infected endothelial cells as a cell type responsible for Treg cell induction in rats.…”

“…In the lungs of SEOV-infected rats, the frequency of Treg cells significantly increases after the SEOV RNA load peaks during the acute phase of infection, suggesting the induction of Treg cells during the persistent phase of infection might be dependent on SEOV replication in cells, including AMs and lung endothelial cells, during the acute phase of infection (19). Macrophages and endothelial cells can induce CD4 ϩ T cells into Treg cells following appropriate cell (e.g., MHC-II engagement and costimulation and PD-1-PD-L1 pathway activation) or cytokine (e.g., presence of TGF-␤) stimulation (38,41,72). Coculturing of naïve CD4 ϩ T cells with infected LMVECs induced CD4 ϩ T cells to differentiate into Treg cells.…”

“…Both macrophages and endothelial cells are capable of inducing naïve CD4 ϩ T cells to differentiate into Treg cells (1,38,41,72). Whether hantaviruses productively infect AMs or endothelial cells in reservoir hosts and whether infection of these cells creates a regulatory environment necessary for induction of Treg cells during persistent hantavirus infection have not been determined and formed the basis for the current studies.…”

Effector Mechanisms of Rejection

“…In a recent review, Taflin et al (2011Taflin et al ( , 2012 described how in the context of inflammation, such as observed in transplantation, endothelial cells are activated by proinflammatory cytokines and TLR ligands. This activation leads to memory CD4 þ T-cell proliferation and Th1/Th17 expansion by endothelial cell secretion of proinflammatory cytokines and chemokines (such as CXCL10, IL-6, and IL-1a) and overexpression of costimulatory molecules (such as LFA-3 or OX-40L) or adhesion molecules (such as ICAM-1) (Griffin et al 2012).…”