TRANSFERRIN, DERIVED FROM AN OKT8-POSITIVE SUBPOPULATION OF LYMPHOCYTES-T SUPPRESSES THE PRODUCTION OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATORY FACTORS FROM MITOGEN-ACTIVATED LYMPHOCYTES-T

Abstract

Purified human transferrin, when saturated with Fe or Zn, decreased the production of granulocyte-macrophage colony-stimulating factors (GM-CSF) by human T lymphocytes that had been stimulated by phytohemagglutin or concanavalin A. The Fe-saturated transferrin was more active than the Zn-saturated transferrin. This effect was not seen for Cu-saturated transferrin or for apotransferrin, and the inhibitory effect was seen whether production of GM-CSF occurred in the absence or presence of serum. If the lymphocytes were pretreated with monoclonal antibody against transferrin receptors, no suppressive effect with transferrin was seen. Transferrin did not have a direct effect on the granulocyte-macrophages colony or cluster-forming cells (CFU-GM) or on preformed GM-CSF. Transferrin-inhibitory activity was produced and released only from a subpopulation of T lymphocytes that had the OKT8+ antigenic phenotype. Release of this activity from OKT8+ lymphocytes, into culture medium at 37.degree. C, was first detected after 6-17 h, but the capacity of the GM-CSF-producing lymphocytes to respond to transferrin-inhibitory activity was apparent only within the first 3 h of placing the lymphocytes at 37.degree. C. The studies demonstrate feedback interactions confined to cells of the T lymphocyte lineage that may be of relevance to the regulation of myelopoiesis.