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.