Recent advances using transgenic animals or exogenous complement inhibitors
have demonstrated prevention of hyperacute rejection of vascularized organ
s, but not graft loss due to acute vascular rejection. Using various wild-t
ype and cytokine-deficient mice strains, we have examined the mechanisms of
acute vascular rejection. C57BL/6 mice deficient in interleukin12 or gamma
interferon showed faster acute vascular rejection than did wild-type mice.
Furthermore, mice defective in B-cell development showed no acute vascular
rejection. These results demonstrate that the axis of interleukin 12 and g
amma interferon provides a survival advantage in vascularized xenografts by
delaying or preventing acute vascular rejection caused by a B cell-depende
nt mechanism.