PROLONGATION OF ISLET ALLOGRAFT SURVIVAL WITH AN ANTIBODY TO VASCULARCELL-ADHESION MOLECULE-1

Background. the purpose of this study was to determine whether an anti body to vascular cell adhesion molecule 1 (VCAM1) prolongs the surviva l of neovascularized pancreatic islet allografts. Methods. We treated CBA (H-2(k)) recipients of BALB/c (H-2(d)) islet allografts with anti- VCAM1 antibody (400 mu g/day for 20 days). Sensitized recipients of is let grafts also were treated with anti-VCAM1. To study mechanism we pe rformed mixed lymphocyte reactions (MLRs) with anti-VCAM1 and studied the graft infiltrate in treated recipients. Results. Anti-VCAM1-treate d CBA recipients showed prolonged graft survival with indefinite survi val in five of nine cases. Anti-VCAM1 prevented proliferation in an ML R but not when added 36 hours after the beginning of the MLR. Anti-VCA M1 did not prolong allograft survival in sensitized recipients and did not prevent lymphocytic infiltration of the graft at 7 days. Conclusi ons. Anti-VCAM1 prolongs allograft survival in neovascularized islets in which the donor vascular endothelium plays little or no role in imm unogenicity. VCAM1 appears to the important in the afferent phase (lym phocyte activation) of the allograft response. Once activated, either late in an MLR or in sensitized recipients, lymphocytes are not depend ent on VCAM1 for function. Finally, anti-VCAM1 does not appear to affe ct the homing of lymphocytes to the allograft.