Mechanism of action of cyclosporine in preventing cardiac allograft rejection. I. Rate of entry of lymphocytes from the blood, fibrin deposition, and expression of Ia antigens on infiltrating cells.

The rate of entry of 3H-leucine-labeled lymphocytes was monitored in cyclosporine (CsA) treated or untreated rats that had received a cardiac allograft 5 days previously. In the untreated recipients there was a preferential localization of labeled cells in the graft heart compared with the native heart, which was evident within the first hour as well as at 3 and 24 hr after injection. In CsA-treated recipients, the rate and extent of entry of lymphocytes in the graft heart was not substantially different from the native heart. Fibrin deposition within allografts, thought to be a consequence of T cell activation, was substantially reduced by CsA treatment of the recipients. A double immunoenzyme staining technique was used to identify Ia-positive macrophages and Ia-positive T cells in cryostat sections of grafts: although the number of macrophages and T cells was reduced in CsA treated recipients, there was no difference in the extent to which these cells were Ia-positive.