Cardiac Allograft Unresponsiveness Using a Posttransplant Strategy: Characterization of the Graft Infiltrate

Abstract We evaluated a combined posttransplant strategy using antilymphocyte serum (ALS) at time of engraftment followed by low dose total lymphoid irradiation (TLI) and donor bone marrow cell (BMC) inoculation administered either intrathymically (IT) or intravenously (IV) in the vigorously rejecting strain combination DA into Lew recipients. Allograft survival was significantly prolonged with administration of ALS in combination with TLI and IT (105 ± 28.6 days) or IV (106.8 ± 28.6 days) BMC compared to administration of ALS combined with either TLI (17.8 ± 0.4 days) or BMC (9.0 ± 0.0 days), or TLI combined with BMC (11.5 ± 0.5 days) ( P 100 days posttransplant) was evaluated using nonisotopic in situ hybridization. A similar cytokine profile was demonstrated in allograft tissue compared to naive and isograft tissue, except for a slight increase in IL-2 ( P P = NS, other groups). In summary, unresponsiveness was induced in a high-responder strain combination using a combined posttransplant strategy of ALS, TLI, and donor antigen either IT or IV. The cytokine profile of the graft infiltrating cells was similar to that of normal tissue. Unresponsiveness may be the result of functional inactivation of these cells.