Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow.
We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.
D000818:Animals; D001853:Bone Marrow / Q000502:physiology*; D001854:Bone Marrow Cells; D002455:Cell Division; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007377:Interleukin-3 / Q000494:pharmacology; D008175:Lung Neoplasms; D051379:Mice; D008810:Mice, Inbred C57BL; D009500:Neutralization Tests; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000494:pharmacology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis / Q000502:physiology*; D014407:Tumor Cells, Cultured
D007377:Interleukin-3; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D012313:RNA; D007371:Interferon-gamma