PROLIFERATION AND ACTIVATION OF ENDOMYOCARDIUM-INFILTRATING LYMPHOCYTES DERIVED FROM ALLOGRAFTED HUMAN HEARTS REQUIRE IL-4

The regulatory mechanisms implicated in the development of human allog raft rejection are still poorly understood and further studies are req uired for a better understanding of rejection events. We have studied the capacity of endomyocardium-infiltrating lymphocytes (EIL) to produ ce IL-4 and its relation with rejection episodes. We have found that t he IL-4 production levels are closely related with histological reject ion. Interestingly IL-4 does not synergize with IL-2 effects in the pr oliferative response in vitro. Indeed, addition of anti-IL-4-neutraliz ing mAb to the cultures strongly inhibits T-lymphocyte proliferation, even in the presence of rIL-2. These findings clearly support an impor tant contribution of IL-4 to the regulation of allogeneic immune respo nse leading to transplanted human heart rejection.