title: Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor beta.
abstract: Normal bone marrow cells become immunosuppressive when cultured with supernatants of metastatic Lewis lung carcinoma (LLC-LN7) cells. The suppressor-inducing activities in the LLC-LN7 supernatants are interleukin-3 and granulocyte/macrophage-colony-stimulating factor. In the present study, the mechanisms by which these induced suppressor cells (LLCsup-BM) mediate their immunosuppression were investigated. The suppression by LLCsup-BM of splenic concanavalin CA blastogenesis was not dependent on cell contact since immunosuppression occurred regardless of whether the LLCsup-BM were separated from the responder spleen cells by a permeable membrane or if the LLCsup-BM were cocultured with the spleen cells. Culture supernatants of LLCsup-BM also inhibited T cell blastogenesis, being more suppressive than were supernatants of control bone marrow cells, which had been precultured with medium. The suppression by the soluble inhibitors elaborated from the LLCsup-BM was not restricted to the inhibition of T cell function as the supernatants also inhibited the natural killer activity of normal spleen cells. Studies to determine the identity of the suppressive activity produced by the LLCsup-BM showed increased levels of transforming growth factor beta (TGF beta) in their supernatants. Immunosuppressive bone marrow and spleen cells obtained from mice bearing metastatic LLC-LN7 tumors also secreted more TGF beta than did the cells obtained from normal mice. When anti-TGF beta antibodies were added to the LLCsup-BM supernatants, the suppressive activity was diminished. These results suggest that the LLCsup-BM mediate at least part of their immunosuppression through production of TGF beta.
authors.affiliation: Department of Research Services, Hines V. A. Hospital, IL 60141.
authors.forename: M R
authors.initials: MR
authors.lastname: Young
authors.forename: M A
authors.initials: MA
authors.lastname: Wright
authors.forename: M
authors.initials: M
authors.lastname: Coogan
authors.forename: M E
authors.initials: ME
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Bagash
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D002277:Carcinoma / Q000503:physiopathology*; D003470:Culture Media; D016207:Cytokines / Q000502:physiology*; D007108:Immune Tolerance; D008213:Lymphocyte Activation; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D003470:Culture Media; D016207:Cytokines; D016212:Transforming Growth Factor beta