ILT3+ ILT4+ tolerogenic endothelial cells in transplantation

T cells can recognize allogeneic major histocompatibility complex (MHC) antigens by two distinct routes: either directly as intact molecules or indirectly as processed peptides presented by syngeneic antigen-presenting cells (APC). The graft endothelium plays an important role in rejection eliciting and serving as a target of T cells activated via the direct and/or indirect allorecognition pathway. Recent evidence demonstrates, however, that endothelial cells are also endowed with the capacity to downregulate alloreactivity inducing tolerogenic responses. Similar to professional APC (such as dendritic cells), endothelial cells express high levels of inhibitory receptors (ILT3 and ILT4 in humans and PIR-B in rodents) and low levels of costimulatory and adhesion molecules upon interaction with allospecific CD8 T suppressor cells or exposure to inhibitory cytokines. Because of the importance of endothelial cells in the activation and control of T cell reactivity, understanding of their biology is crucial for the development of new strategies for induction of transplantation tolerance and treatment of cancer, chronic infection, and autoimmunity.