Neutropenia in three patients with rheumatic disorders. Suppression of granulopoiesis by control-sensitive thymus-dependent lymphocytes

Abstract

A man with polymyalgia rheumatica (patient 1) and two patients (2 and 3) with Felty's syndrome had neutropenia at the time of diagnosis. Bone marrow samples in each patient were cellular but showed an "arrest" of granulocyte maturation at the myelocyte stage. Agar colony growth of marrow cells from each patient was subnormal but increased after removal of sheep erythrocytes rosette-forming cells (thymus-dependent [T] cells) from marrow cell suspensions before culture. Preincubation of marrow cells with cortisol also enhanced colony growth. Maximum enhancement with cortisol occurred at 1 mM (patient 1), 1 microM (patient 2), and 10 nM (patient 3). Cortisol failed to enhance colony growth after removal of T cells from marrow cell suspensions. Peripheral blood lymphocytes (PBL) and PBL-conditioned medium from all three patients inhibited colony growth of normal human marrow cells. Cortisol treatment of PBL or T depletion from PBL abrogated the inhibition in coculture and with conditioned medium. Prednisone therapy resulted in the disappearance of suppressor T-cell function concomitant with hematologic improvement in patients 2 and 3, but suppressor T cells persisted in patient 1, who did not respond to prednisone. We conclude that cortisol-sensitive T lymphocytes inhibited granulopoiesis in vitro probably by elaboration of a soluble factor or factors. Our results suggest (a) that neutropenia in these patients resulted, at least in part, from T-cell suppression of granulopoiesis, (b) that the effectiveness of prednisone therapy was a result of its inhibition of suppressor T cells, and (c) that responses to glucocorticoid therapy may be predicted in such patients with the agar culture technique and cortisol dose response in vitro.