caa a22 4500 469073519 CHVBK 20180323132928.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF01741049 doi (NATIONALLICENCE)springer-10.1007/BF01741049 Tumor-derived cytokines induce bone marrow suppressor cells that mediate immunosuppression through transforming growth factor β [Elektronische Daten] [M. Young, Mark Wright, Michael Coogan, Melvin Young, Jamila Bagash] Summary: Normal bone marrow cells become immunosuppressive when cultured with supernatants of metastatic Lewis lung carcinoma (LLC-LN7) cells. The suppressorinducing 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 β (TGFβ) in their supernatants. Immunosuppressive bone marrow and spleen cells obtained from mice bearing metastatic LLC-LN7 tumors also secreted more TGFβ than did the cells obtained from normal mice. When anti-TGFβ 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 TGFβ. Springer-Verlag, 1992 Lewis lung carcinoma nationallicence TGFβ nationallicence Bone marrow nationallicence Immunosuppressor nationallicence Young M. Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut Wright Mark Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut Coogan Michael Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut Young Melvin Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut Bagash Jamila Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut Cancer Immunology, Immunotherapy Springer-Verlag 35/1(1992-01-01), 14-18 0340-7004 35:1<14 1992 35 262 https://doi.org/10.1007/BF01741049 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741049 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Young M. Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut NATIONALLICENCE 700 1- Wright Mark Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut NATIONALLICENCE 700 1- Coogan Michael Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut NATIONALLICENCE 700 1- Young Melvin Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut NATIONALLICENCE 700 1- Bagash Jamila Department of Research Services, Hines V. A. Hospital, 60 141, Hines, IL, USA aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/1(1992-01-01), 14-18 0340-7004 35:1<14 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer