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Transforming growth factor‐β is the major mediator of natural suppressor cells derived from normal bone marrow
Author(s) -
Moore Steven C.,
Shaw Michael A.,
Soderberg Lee S. F.
Publication year - 1992
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.52.6.596
Subject(s) - transforming growth factor , biology , cytokine , bone marrow , growth factor , cell culture , microbiology and biotechnology , mediator , cell growth , immunology , cancer research , biochemistry , receptor , genetics
We previously reported that murine bone marrow cells activated by interleukin‐3 (IL‐3) or granu‐ locyte‐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‐β (7GF‐β), 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‐ β‐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‐β and rIL‐3 induced a sevenfold increase in TGF‐β transcription. Finally, neutralizing anti‐TGF‐β antibody inhibited the suppressive activity of the supernates, indicating that TGF‐β was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.