Prednisone-responsive aplastic anemia: a mechanism of glucocorticoid action.

We performed serial agar cultures (CFU-C) using marrow cells from a patient with prednisone-responsive aplastic anemia and from five patients with prednisone-resistant aplasia. Colony growth was decreased in all patients. Cortisol (10(-7)-10(-4)M) significantly enhanced colony growth in the prednisone-responsive patient but fauled to enhance colony growth in the remaining five patients. Further studies in the responsive patient indicated that (1) colony growth was enhanced by depleting T lymphocytes from the marrow cells, (2) colon growth T-depleted marrow cells was inhibited by autologous peripheral blood lymphocytes (PBL), (3) cortisol failed to enhance colony growth of T-depleted marrow cells, (4) PBL and PBL-conditioned medium inhibited colony growth of both autologous and allogeneic marrow cells, but neither cortisol-treated PBL nor T-depleted PBL were inhibitory. Serial cultures in the responsive patient showed that colony growth normalized during remission when "suppressor" cells were absent and that colony growth was subnormal during a later relapse when cortisol-resistant "suppressor" cells were present. Therefore, in this prednisone-responsive patient, cortisol-sensitive T lymphocytes suppressed granulopoiesis in vitro. Our observations suggest that aplastic anemia in this patient is immunologically mediated and that prednisone therapy enhanced hemopoiesis in vivo by inhibiting the "suppressor" T lymphocytes.