Human T cells infiltrate and injure pig coronary artery grafts with activated but not quiescent endothelium in immunodeficient mouse hosts

Background. We have previously demonstrated that human artery grafts transp lanted to immunodeficient mice are infiltrated and injured by unsensitized allogeneic human T cells. We extended our investigations to human anti-porc ine xenoresponses in this model. Methods. Pig coronary artery segments were interposed into the infrarenal a orta of severe combined immunodeficiency/beige mice. After 7 days, certain recipients were reconstituted with human leukocytes and/or treated with pro inflammatory cytokines, The grafts were harvested after 1-70 days and exami ned by histology, immunohistochemistry, and morphometry. Results, Pig artery grafts from untreated mice had no evidence of injury, l eukocytic infiltrate, or endothelial cell activation up to 70 days postoper atively, despite deposition of murine complement, Host reconstitution with human peripheral blood mononuclear cells resulted in a discrete population of circulating T cells that did not infiltrate or injure the grafts up to 2 8 days after adoptive transfer, Administration of porcine interferon-gamma for up to 28 days sustained the expression of graft vascular cell adhesion molecule-1 and major histocompatibility complex antigens, but did not initi ate recruitment of human leukocytes, In contrast, treatment with human tumo r necrosis factor for 7 days induced the de novo expression of porcine E-se lectin by graft endothelial cells and elicited human T cell infiltration an d human peripheral blood mononuclear cell-dependent vascular injury. Conclusions. The human peripheral blood mononuclear cell-severe combined im munodeficiency/beige mouse model identifies a significant difference betwee n human T cell allogeneic and xenogeneic responses in vivo. Xenografts with quiescent endothelium are not infiltrated or injured by T cells under the same conditions in which allografts are rejected. Activation of pig coronar y artery endothelial cells by human tumor necrosis factor, but not porcine interferon-gamma, elicits cellular xenoresponses.