EVIDENCE OF NONINVOLVEMENT OF SWINE MHC CLASS-II IN THE IN-VITRO PROLIFERATIVE RESPONSE OF HUMAN-LYMPHOCYTES TO PORCINE ENDOTHELIAL-CELLS

Successful pig-to-human xenotransplantation may expose swine endotheli um to the human immune system. Since endothelial MHC class ZI expressi on is crucial in the genesis of an allogeneic lymphocyte response, the involvement of porcine MHC (SLA) class II molecules in the induction of human lymphocyte proliferation was studied. When cocultured with a confluent monolayer of irradiated porcine aortic endothelial cells (PA EC), human peripheral blood mononuclear cells (PBMC) incorporated trit iated thymidine. Monocyte depletion strongly reduced the magnitude of the lymphocyte proliferative response. Resting cultured PAEC were SLA class II-negative and an induction of these molecules during the xenog eneic mixed lymphocyte endothelial cell culture (XMLEC) was not observ ed. Moreover, the addition of an antibody directed against the SLA-DR molecule was without effect. Lymphocyte proliferation was also studied in response to SLA class II-positive stimulating cells-either human T NF-alpha-stimulated PAEC or porcine splenocytes. Induction of SLA clas s II molecules on PAEC had no effect on the human PBMC proliferative r esponse. Moreover, human PBMC did not proliferate in response to porci ne splenocytes. These results suggest (1) that SLA class II molecules are not involved in the induction of the human lymphocyte proliferativ e response and (2) that the endothelial nature of the stimulating cell s plays a key role in this proliferation.