Regulation of the CD4+ T cell allo-immune response by endothelial cells

Recent studies have revealed the presence of pro-inflammatory and/or regulatory CD4+ T cells within allografts promoting either graft rejection or tolerance. Histological evidence has identified the microvascular endothelium as the primary site of allograft damage as it is the first site of encounter with the recipient’s immune system. The initial view of the human endothelial cell inducing an effector Th1 response leading to graft rejection has been extended by recent results which demonstrate the endothelial cell ability to generate other CD4+ T cell sub-populations including Th17 and Treg cells. In the transplantation setting, the allo-reactivity of the endothelium with the CD4+ T cell populations is likely to depend upon multiple factors including the vascular origin of the endothelial cell, the cytokine environment, the presence or absence of pro-inflammatory stimuli including ligands of Toll like receptors and alloantibodies. This review provides an update on the characteristics of the endothelial cell activation of the CD4+ T cell response and an analysis of the factors, which can modify this activity in favor of either graft rejection or tolerance.