Daily in vivo treatment of murine H-2d-->H-2b cardiac allograft recipi
ents with 400 mug/day i.p. of M/K-2, a mAb to the endothelial adhesion
molecule VCAM-1, resulted in prolongation of graft survival. The surv
iving allografts showed little of the histologic changes observed in a
cutely rejecting control allografts. When antibody treatment was disco
ntinued after 20 days, grafts continued to function for at least 40 mo
re days. This was approximately 30 days after mAb was no longer detect
able by ELISA in the circulation, or by immunoperoxidase staining at t
he graft site. The most notable feature of grafts that survived 60 day
s was the presence of mild interstitial fibrosis. Endothelial reactivi
ty was minimal with the mAbs MECA-32 and M/K-2, which have been used i
n previous studies to visualize the extensive endothelial inflammation
that develops during untreated acute rejection. There was a mild cell
ular infiltrate containing T cells, but few macrophages. However, infi
ltrating T cells appeared to be inactive in that IL-2R+ cells were imm
unohistologically undetectable and mRNA for IL-2, IL-4, or IFN-gamma w
as undetectable by polymerase chain reaction. In general, the immunolo
gic conditions in these long-term grafts differed from those seen in n
ormal cardiac tissue, cardiac isografts, or cardiac allografts. These
data demonstrate that M/K-2 mAb can suppress cardiac allograft rejecti
on and induce long-term graft acceptance. This graft survival appears
to be associated with the development of a unique state of immunity at
the graft site.