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-Ig and costimulate human T cells by both the CD2 and CD28 pathways. In contrast, HUVECs do not bind CTLA-4-Ig and only use the CD2 pathway.
Murray
A G
AG
Molecular Cardiobiology Program, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Khodadoust
M M
MM
Pober
J S
JS
Bothwell
A L
AL
D000818:Animals; D017951:Antigen Presentation; D015478:Antigens, Heterophile / Q000378:metabolism; D018801:CD2 Antigens / Q000378:metabolism; D018106:CD28 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008024:Ligands; D008213:Lymphocyte Activation; D013045:Species Specificity; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology*
D015478:Antigens, Heterophile; D018801:CD2 Antigens; D018106:CD28 Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D008024:Ligands