INFILTRATION PATTERNS OF MACROPHAGES AND LYMPHOCYTES IN CHRONICALLY REJECTING RAT-KIDNEY ALLOGRAFTS

The migration of circulating leukocytes to sites of inflammation or an tigen is based, at least in part, on the activities of adhesion molecu les. In the context of organ transplantation, some of these have been shown to be upregulated during acute allograft rejection. As their rol e during chronic rejection has not been examined, we have used an esta blished rat model to compare sequentially the presence of host cells w ithin the grafts, as defined immunohistologically, with patterns of in vitro leukocyte binding and their dependence upon particular adhesion molecules. Various donor populations of peripheral blood lymphocytes (PBL), lymph node lymphocytes (LNL), and splenic monocytes were intera cted with snap-frozen sections of allografted, isografted, and native kidneys at serial intervals up to 24 weeks after transplantation. Mono cyte binding in the allografts rose at 8 weeks and peaked at 12 weeks, a period preceding the maximum numbers of macrophages noted immunohis tologically in the chronically rejecting grafts at 16 weeks. Lymphocyt e binding and infiltration patterns were similar, remaining stable thr oughout the follow-up period and consistently greater than those noted in isografts. In vitro binding of the monocytes was inhibited by mAbs against ICAM-1, LFA-1, CD18, and MAC-1; MAC-1 did not influence lymph ocyte binding, although the other mAbs were effective. We conclude tha t adhesion molecules are responsible, at least in part, for patterns o f cell populations infiltrating chronically rejecting renal allografts .