CELLULAR PROLIFERATION AT THE SITE OF ORGAN ALLOGRAFTS AND THE INFLUENCE OF IMMUNOSUPPRESSIVE THERAPY

Abstract

In this study we investigated cellular proliferation of T cells and macrophages at the site of rat cardiac allografts and determined the influence of immunosuppressive therapy on the proliferative characteristics of these cell types. A bromodeoxyuridine-labeling technique was used that allowed both the accurate detection of proliferative activity and the phenotype characterization of cellular infiltrates with grafted tissues. In untreated recipients (BN .fwdarw. Lewis), T cytotoxic/suppressor cells as well as T helper cells showed proliferative activity at the site of the graft. The percentage of OX8-positive cells with the graft that showed proliferation ranged from 15% to 37%. The percentage of W3/25-positive cells within the graft that showed proliferation ranged from 25% to 30%. In contrast, macrophages hardly showed proliferative activity within the graft; only 1-4% of the macrophages stained positive for bromodeoxyuridine. From these observations it is concluded that the graft serves as a nonlymphoid tissue site, wherein lymphocytes can freely proliferate and expand. To study the influence of immunosuppressive therapy on cellular proliferation, the steroid budesonide, 120 .mu.g/kg/day, was administered for 13 days (MST, 20 days). During effective immunosuppressive therapy, still a remarkable amount of infiltrating cells was present within the grafts. Moreover, immunosuppressive treatment did not primarily appear to affect the proliferative capacity of the individual cell types. OX8-positive cell as well as W3/25-positive cells clearly showed proliferative activity within the treated grafts. However, despite the presence of these proliferative cells, signs of graft destruction were absent during immunosuppressive therapy. This finding may shed new light on the effect of steroids at the site of the graft and their role in the prevention of tissue destruction.