PORCINE AORTIC ENDOTHELIAL-CELLS ACTIVATE HUMAN T-CELLS - DIRECT PRESENTATION OF MHC ANTIGENS AND COSTIMULATION BY LIGANDS FOR HUMAN CD2 AND CD28

We examined the human xenoresponse to cultured porcine aortic endothelial cells (PAECs). Human CD8(+) T cells proliferate to resting MHC class I-positive PAECs. CD4(+) T cells proliferate after MHC class II molecules are induced with swine interferon-gamma. These responses are greater than corresponding allogeneic responses to human umbilical vein endothelial cells (HUVECs). Limiting dilution analysis shows a 10-fold higher frequency of xenoreactive than alloreactive anti-endothelial lymphocytes. Species-specific monoclonal antibodies suggest that PAECs directly present swine MHC antigens to human T cells and that human CD4 and CD8 molecules participate in this interaction. Furthermore, PAECs bind CTLA-4-lg and costimulate human T cells by both the CD2 and CD28 pathways. In contrast, HUVECs do not bind CTLA-4-lg and only use the CD2 pathway.