Antigen-specific suppressor macrophages induced by culture with cyclosporine A plus acetylcholine receptor.

Suppressor cells specific for the acetylcholine receptor (AChR) can readily be induced by culturing spleen cells from rats with experimental autoimmune myasthenia gravis in medium containing cyclosporine A plus AChR. We describe here the purification and characterization of novel antigen-specific suppressor cells, which appear to be macrophages, from these cultures. The cells were adherent to plastic, very large, and of low buoyant density. These properties were used to enrich the cells, first by adherence, followed by centrifugation on discontinuous Percoll density gradients. The enriched large suppressor cells (LSC) were shown to be potent suppressors of secondary immune responses to AChR, including both lymphoproliferation and antibody production. Furthermore, the LSC exhibited antigen specificity of suppression: LSC induced with AChR suppressed secondary antibody responses to AChR significantly more than to an unrelated antigen, keyhole limpet hemocyanin (KLH). In reciprocal experiments, LSC induced with KLH suppressed KLH responses significantly more than AChR responses. The LSC exhibited the morphologic, enzymatic, phenotypic, and radioresistance characteristics of macrophages. They were neither lymphocytes nor NK cells as defined by phenotypic and functional properties, respectively. Several possible mechanisms are postulated to explain how these remarkable cells may acquire antigen specificity.