Yz. Tu et al., REJECTION OF SPONTANEOUSLY ACCEPTED RAT-LIVER ALLOGRAFTS WITH RECIPIENT INTERLEUKIN-2 TREATMENT OR DONOR IRRADIATION, Transplantation, 63(2), 1997, pp. 177-181
While MHC incompatible DA (RT1(a)) to Lewis (RT1(1), LEW) rat liver al
lografts are acutely rejected, the reciprocal LEW to DA liver grafts a
re spontaneously accepted, The mechanism of this acceptance remains un
clear, We evaluated the effect of donor treatment with total body irra
diation (TBI) or gadolinium chloride (GdCl3), and recipient treatment
with exogenous IL-2 after transplantation on the survival of the spont
aneously accepted liver grafts, Male LEW and DA rats were used as dono
rs and recipients for orthotopic liver allo- or iso-graft transplants,
The LEW liver donor was treated by TBI (10 gray) 7 days before transp
lantation, or LEW donor Kupffer cell phagocytosis was blocked with GdC
l3 (7 mg/kg) on days -2 and -1 pretransplant. In an attempt to reverse
LEW liver graft acceptance, 180,000 units human IL-2 (hIL-2) were adm
inistered daily IP to the DA liver recipients from days 1 to 7 after l
iver grafting, While untreated LEW recipients rejected DA liver grafts
within 13 days, DA recipients accepted LEW livers indefinitely (>302
days), In contrast, irradiation of the LEW liver donor prevented the s
pontaneous acceptance by DA recipients, and resulted in acute rejectio
n of the liver grafts in 9-20 days, However, spontaneous graft toleran
ce was restored by parking the irradiated LEW donor Liver in naive LEW
rats for 48 hr before retransplantation to DA recipients (>50 days),
When LEW donors were treated with GdCl3, which is known to block Kupff
er cell phagocytosis and antigen processing, the spontaneous acceptanc
e of the LEW liver grafts by DA recipients was unaffected, However, wh
en exogenous rhIL-2 was given daily, LEW liver allografts were rejecte
d by the DA recipients, The resulting liver failure correlated with a
progressive increase in serum bilirubin and the development of a predo
minantly lymphocytic portal tract infiltration, bile duct epithelial d
amage, and portal vein endothelitis, which is consistent with acute al
lograft rejection, LEW and DA recipients of liver isografts developed
no toxicity and survived indefinitely (>100 days) when treated with th
e same dose of IL-2, These results indicate that spontaneous rat liver
allograft acceptance is associated with the presence of radiosensitiv
e cells in the donor liver that may interact with recipient T cells to
inhibit (Th1) production of IL-2.