Macrophage-related suppressor cells in human renal transplant recipients

In this study 66 renal transplant recipients were studied by in vitro immunologic monitoring assays in an attempt to delineate some immune reactivity parameters which migh explain the successful long-term survival of HLA incompatible allografts. Ninety percent of the recipients were found to be responsive to their specific donors in one-way mixed lymphocyte culture assays, indicating the presence of antigen reactive proliferating T cells. In contrast, studies of the in vitro generation of cytotoxic T cells showed that 73% of the long-term recipients demonstrated a marked hyporesponsiveness to the donor in cell-mediated lympholysis (CML) assays. Longitudinal studies indicated that specific CML hyporesponsiveness to the donor developed after transplantion. In the majority of recipients, CML hyporesponsiveness could be related to a suppressor cell phenomenon, since recipient mononuculear cells specifically suppressed the CML reactivity of third-party cells to the donor. Recipient CML hyporesponsiveness to the donor could be abrogated by removal of recipient adherent cells, most of which were monocytes or macrophages. The suppressor cell effect on CML is postulated to be related to macrophages which are either acting independently or under the regulation of suppressor T cells. These studies are among the first to suggest that suppressor cell regulation of relevant effector T cell activity may be important in the facilitation of successful human renal transplantation.