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Direct cytotoxic response of human lymphocytes to porcine PHA-lymphoblasts and lymphocytes
1Department of Clinical Immunology, Odense University Hospital, Denmark.
Transplantation of cells and organs from pigs to human beings offers potential treatment for medical conditions such as diabetes, kidney and heart failure, and Parkinson's disease. When the antibody-mediated hyperacute rejection barrier is overcome, a xenograft may not be treated as an allograft by the human immune system. Without prior culture with porcine cells, human lymphocytes are cytotoxic to some porcine cells. Our aim was to functionally characterize this direct cytotoxic response to porcine PHA-lymphoblasts and lymphocytes. Peripheral blood mononuclear cells from seven of eight human beings were cytotoxic to porcine PHA-lymphoblasts in bulk chromium-release assays, but not to the porcine lymphocytes from which the PHA-lymphoblasts were derived. The NK cell-sensitive cell line K562 only partly blocked the response to the PHA-lymphoblasts. IL-2-expanded clones of human lymphocytes were able to discriminate between PHA-lymphoblasts from two pigs and unable to lyse K562. When using IL-2 to make the anti-porcine cells proliferate under limiting dilution conditions, the proliferation and/or function of these cells did not conform to single-hit kinetics. All the observations from experiments with cells in bulk cultures and as short-term clones suggest that the direct cytotoxic response of human lymphocytes to porcine cells is heterogeneous and composed of a small population of in vivo-activated T cells as well as NK cells.
Transplantation of cells and organs from pigs to human beings offers potential treatment for medical conditions such as diabetes, kidney and heart failure, and Parkinson's disease. When the antibody-mediated hyperacute rejection barrier is overcome, a xenograft may not be treated as an allograft by the human immune system. Without prior culture with porcine cells, human lymphocytes are cytotoxic to some porcine cells. Our aim was to functionally characterize this direct cytotoxic response to porcine PHA-lymphoblasts and lymphocytes. Peripheral blood mononuclear cells from seven of eight human beings were cytotoxic to porcine PHA-lymphoblasts in bulk chromium-release assays, but not to the porcine lymphocytes from which the PHA-lymphoblasts were derived. The NK cell-sensitive cell line K562 only partly blocked the response to the PHA-lymphoblasts. IL-2-expanded clones of human lymphocytes were able to discriminate between PHA-lymphoblasts from two pigs and unable to lyse K562. When using IL-2 to make the anti-porcine cells proliferate under limiting dilution conditions, the proliferation and/or function of these cells did not conform to single-hit kinetics. All the observations from experiments with cells in bulk cultures and as short-term clones suggest that the direct cytotoxic response of human lymphocytes to porcine cells is heterogeneous and composed of a small population of in vivo-activated T cells as well as NK cells.