Allogeneic and xenogeneic interactions between endothelial cells and human T cells during transplant rejection

Human and porcine endothelial cells express on their cell surfaces many of the molecules, which can cause activation of T cells. Of particular importance is expression of Major Class II Histocompatibilty (HLA- DR DP and DQ) molecules which are essential for activation of CD4+ T cells and subsequent maturation of the various effector mechanisms leading to allograft rejection. Cells which cause activation of resting CD4+ T cells are called Antigen Presenting Cells (APCs); the essential pre-requisite for APCs are expression of MHC class II molecules and accessory molecules which interact with T ligands. It is established that dendritic cells, monocytes and B cells are APC but in humans many parenchymal cells such as fibroblasts, smooth muscle cells and epithelial cells can be induced to express MHC class II antigens by IFN gamma. Data is presented which shows that both human and porcine endothelial cells, but not other parenchymal cells, act as APC and stimulate resting CD4+ T cells, however they utilise different second signals. Human and endothelial cells use LFA/3 whereas porcine endothelial cells present CD86 to human T cells. Porcine CD86 and porcine MHC class II molecules are recognised by human T cells and results in vigorous T cell activation and production of Interleukin-2. There is some compatibility between human cytokines and porcine endothelial cells; thus IFN gamma is species specific but human TNF alpha induces MHC class II, VCAM-1, and CD86 on porcine endothelial cells. It is highly likely that human and porcine endothelial cells will directly interact and activate recipient T cells after allogeneic or xenogeneic implantation.