Recognition of porcine major histocompatibility complex class I antigens by human CD8+ cytolytic T cell clones.
To evaluate the nature of the human cellular immune response to porcine xenoantigens, cytolytic T lymphocyte (CTL) cell lines were generated against porcine aortic endothelial cells (PAEC). After four stimulations, the phenotypes of the T cell lines were primarily CD8+ (79.7+/-19.6%). Natural killer cells were not detected. Functional analysis of the T cell lines showed specific cytotoxicity against syngeneic porcine targets with no lysis of unrelated porcine cells, human cells, or K562, a natural killer target. The major histocompatibility complex (MHC) specificity of this response was confirmed when T cell lines established against PAEC from partially inbred SLAdd miniature swine lysed only PAEC and phytohemagglutinin-stimulated lymphocytes from SLAdd origin but not SLAgg targets. Both CD8+ (7/12) and CD4+ (5/12) T cell clones were generated from the bulk cell lines. All of the CD8+ T cell clones specifically lysed stimulator PAEC and swine leukocyte antigen (SLA)-matched, phytohemagglutinin-stimulated lymphocyte targets but not unrelated porcine targets. CD4+ T cell clones, as expected, showed no lysis of any porcine target cells. The lysis of porcine targets by the human CD8+ cytotoxic T lymphocyte clones was inhibited by monoclonal antibodies against SLA class I antigens and human CD8, which indicates that human CD8+ T cells recognize porcine MHC class I molecules. These results, which show that human T cells differentiate between porcine MHC alleles, have relevance in the clinical application of xenografts.
Shishido
S
S
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Naziruddin
B
B
Howard
T
T
Mohanakumar
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000954:Antigens, Surface / Q000502:physiology; D001011:Aorta / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D013552:Swine; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014183:Transplantation, Heterologous / Q000276:immunology
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015395:Histocompatibility Antigens Class I