Effect of surrogate tolerogenesis on the vascular rejection of pig heart xenografts.
BACKGROUND
Organ xenografts are fulminantly rejected by antibody-mediated vascular rejection. Surrogate tolerogenesis (ST), the induction of tolerance within the donor, is effective with aorta xenografts. This preliminary study assesses the effect of ST on preformed antibodies and rejection of porcine heart xenografts.


METHODS
Tolerance to the donor pig was induced by infusing recipient marrow into fetal pigs. Later, pig splenocytes were transfused and heterotopic pig hearts transplanted using chimeric or nonchimeric pigs. Anti-pig antibodies were assessed.


RESULTS
With ST alone, xenografts developed cellular rejection at 4-6 days, whereas control grafts developed vascular rejection at 3-4 days (cellular vs. vascular, P<0.03). There was a reduction in preformed antibodies (P<0.03). ST combined with moderate cyclosporine prevented rejection at 9+ and 25 days in sensitized recipients compared with vascular rejection at 0.5-2 days for controls (P<0.07).


CONCLUSIONS
ST seems to provide protection against vascular rejection. The cellular rejection seems sensitive to cyclosporine.
Sudan
D L
DL
Department of Surgery, University of Nebraska Medical Center, Omaha 68198, USA.
Radio
S J
SJ
Matamoros
A
A
Johnson
N D
ND
Shearon
C C
CC
Glogowski
K R
KR
Hill
A C
AC
Goertzen
T C
TC
Fox
I J
IJ
Langnas
A N
AN
Beschorner
W E
WE
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control; D016027:Heart Transplantation / Q000276:immunology; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D011247:Pregnancy; D012756:Sheep; D013154:Spleen / Q000166:cytology; D013552:Swine; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000276:immunology
D007166:Immunosuppressive Agents; D016572:Cyclosporine