The Importance of H-Y Incompatibility in Human Organ Transplantation

SUMMARY As an extension of our first observation in which the peripheral blood lymphocytes of an aplastic amaemia patient with a transplant were able to show HLA-restricted H-Y killing in a cell-mediated lympholysis assay, we report here a second case showing exactly the same phenomenon. A multitransfused woman suffering from aplastic anaemia was shown to have in vitro killing after priming her lymphocytes with her HLA-identical brother. This killing was directed to all male target cells carrying the HLA-A2 antigen. Marginally, killing was also directed to some HLA-A2 female target cells, but this was at a considerably lower level than that directed to male cells. The level of HLA-restricted H-Y killing declined with time. However, it was possible to reactivate the H-Y specific killing by in vitro stimulation with lymphocytes from an HLA-A, -B, and -C-identical, but HLA-D-different male donor. That these findings could be relevant for renal transplantation was supported by renal allograft survival data obtained at 2 years after transplantation. Male allografts from HLA-A2-positive donors in A2-positive females survived for a significantly shorter time than non-A2 male kidneys in non-A2 female recipients. This was only apparent in recipients who produced antileukocyte antibodies.