Analysis of mechanisms in delayed xenograft and cellular rejection in xenotransplant between human and swine

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Humanized severe combined immunodeficient (SCID) mice, which exhibited human immunological environment, were established by administration of human peripheral blood lymphocytes (PBL). This hu-PBL-SCID mice were also demonstrated to involve functional human lymphocyte and immunoglobulin in their circulation. To display the real xenotransplant circumstances from swine graft to human in mouse, swine mesenteric arterior was applied for direct bypass of abdominal aorta in hu-PBL-SCID. Analysis of recovered xenograft revealed human IgM adherence to inner rim and lymphocytes invasion on the endothelium of the xenograft. By blocking the xenoreactive serological response with immuno-absorption, pathological analysis indicated these lymphocytes belonged to human CD3+CD4+ in staining. Next, we tried to determine the optimal time to see the cellular rejection in the severest condition by changing the recovering time of xenograft. Stable model of the cellular rejection were.however, difficult to es … More tablish due to the interindividual differences. Human lymphocytes were unable to be detected in the invasion into swine arterior xenografts. We also tried to contitute the human xenoreactive cell line in vitro by recovering this xenografts to tissue culture using irradiated pig aortic endothlial cell (PAEC) as stimulator and irradiated original human lymphocytes as feeder. This experiment, however, resulted in impossible condition due to contaminations from grafts.Recently Dr.Sasaki, one of our colleagues, showed that human NK cells recognized non-expression of HLA-G ＆ E gene in xenograft and played a role in xenograft rejection (Transplantation 67; 31-37 1999). We tried to indicate this evidence in in vivo system using hu-PBL-SCID mice model. Swine arterior xenogarfts transfected with HLA-G ＆ E gene were recovered from hu-PBL-SCID mice, but no suppressive effect of xenoreactive responses were noted in this experoment. One of our manuscripts containing these results were now (in press). Less