Characterization of human CD55 and CD59 transgenic pigs and kidney xenotransplantation in the pig-to-baboon combination.
New transgenic pigs expressing combinations of regulators of complement activation and other molecules are needed to resist xenograft hyperacute rejection (HAR) and to further analyze and treat xenograft rejection. Double transgenic pigs for human CD55 (hCD55) and human CD59 (hCD59) using the promoter of the human elongation factor 1 alpha gene were generated, and their kidneys were transplanted into nonimmunosuppressed baboons. hCD55 and hCD59 were mainly expressed by the endothelial cells, and these cells showed increased resistance to complement-mediated lysis. Baboons receiving kidneys from hCD55hCD59 pigs survived for 5 and 6 days, and displayed alterations in coagulation. Thrombocytopenia and platelet microthrombi were present within the kidneys. Nontransgenic kidneys showed HAR in less than 2 days. Kidneys from pigs expressing hCD55hCD59 displayed protection against HAR in the absence of immunosuppression. Rejection was associated with coagulopathy leukocyte infiltration and a rebound of anti-alpha Gal antibodies.
Ménoret
Séverine
S
INSERM U437, Institut de Transplantation Et de Recherche en Transplantation and CHU de Nantes, Nantes, France.
Plat
Martine
M
Blancho
Gilles
G
Martinat-Botté
Francoise
F
Bernard
Pierre
P
Karam
Georges
G
Tesson
Laurent
L
Renaudin
Karine
K
Guillouet
Philippe
P
Weill
Bernard
B
Chéreau
Christiane
C
Houdebine
Louis-Marie
LM
Soulillou
Jean-Paul
JP
Terqui
Michel
M
Anegon
Ignacio
I
D000818:Animals; D030801:Animals, Genetically Modified; D018958:CD55 Antigens / Q000235:genetics* / Q000276:immunology; D018957:CD59 Antigens / Q000235:genetics* / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D006801:Humans; D016030:Kidney Transplantation; D010215:Papio; D013552:Swine; D014183:Transplantation, Heterologous
D018958:CD55 Antigens; D018957:CD59 Antigens