Human cell-mediated rejection of porcine xenografts in an immunodeficient mouse model.
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.
Sawada
T
T
Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston 02129, USA.
DellaPelle
P A
PA
Seebach
J D
JD
Sachs
D H
DH
Colvin
R B
RB
Iacomini
J
J
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D012867:Skin / Q000473:pathology; D016038:Skin Transplantation / Q000276:immunology*; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology; D014183:Transplantation, Heterologous / Q000276:immunology*