HUMAN CELL-MEDIATED REJECTION OF PORCINE XENOGRAFTS IN AN IMMUNODEFICIENT MOUSE MODEL1
作者:
Sawada2 Tokihiko,
DellaPelle3 Patricia,
Seebach2,4 Jörg,
Sachs2 David,
Colvin3 Robert,
Iacomini2,5 John,
期刊:
Transplantation
(OVID Available online 1997)
卷期:
Volume 63,
issue 9
页码: 1331-1338
ISSN:0041-1337
年代: 1997
出版商: OVID
数据来源: OVID
摘要:
Background.In this study, we describe the development of a novel experimental system in which rejection of porcine skin grafts by human peripheral blood cells can be studied directly in vivo in immunodeficient mice.Methods.To construct a small animal model of discordant xenograft rejection, recombinase-activating gene-deficient mice (R-) lacking both mature B and T cells were grafted with porcine skin grafts and administered, by adoptive cell transfer, human cells stimulated in vitro with irradiated porcine peripheral blood cells to create Hu-R-mice.Results.R-mice accepted porcine skin grafts indefinitely without the need for immunosuppression. In contrast, Hu-R-mice were able to reject porcine skin grafts. Immunohistochemical analysis of rejecting skin grafts revealed the accumulation of human T cells around dermal porcine vessels and focally in the epidermis. Graft rejection was manifested by vascular endothelial cell proliferation, edema at the dermal-epidermal border, and perivascular hemorrhage. The tissue damage observed in the rejecting grafts was similar to that observed in delayed primate anti-porcine cell-mediated rejection of vascularized organ xenografts.Conclusions.The development and characterization of a small animal model, to study cellular immune responses of human cells to discordant xenografts in vivo, should provide a convenient means for asking mechanistic questions related to discordant xenotransplantation, and may also provide a practical system for testing new approaches designed to prevent xenograft rejection.
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