TREATMENT WITH ANTIVASCULAR CELL-ADHESION MOLECULE-1 MONOCLONAL-ANTIBODY INDUCES LONG-TERM MURINE CARDIAC ALLOGRAFT ACCEPTANCE

Citation
Cg. Orosz et al., TREATMENT WITH ANTIVASCULAR CELL-ADHESION MOLECULE-1 MONOCLONAL-ANTIBODY INDUCES LONG-TERM MURINE CARDIAC ALLOGRAFT ACCEPTANCE, Transplantation, 56(2), 1993, pp. 453-460
Citations number
42
Categorie Soggetti
Immunology,Surgery
Journal title
ISSN journal
00411337
Volume
56
Issue
2
Year of publication
1993
Pages
453 - 460
Database
ISI
SICI code
0041-1337(1993)56:2<453:TWACMM>2.0.ZU;2-J
Abstract
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.