Induction of macrophage suppressor activity by fibrosarcoma‐derived transforming growth factor‐β1: contrasting effects on resting and activated macrophages

• Published in: Journal of leukocyte biology 1995-06, Vol.57 (6), p.919-928
• Main Authors: Alieva, David G., Walker, Thomas M., Elgert, Klaus D.
• Format: Article
• Language: English
• Subjects: nitric oxide; prostaglandin; suppression; tumor necrosais factor‐α; tumors
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/jlb.57.6.919

Tumor‐derived transforming growth factor‐β1 (TGF‐β1) suppresses several immune responses. Because tumor growth induces macrophage (mφ) suppressor activity, we determined whether murine fibrosarcoma‐derived TGF‐β1 contributed to mφ‐mediated suppression of autoantigen‐ and alloantigen‐stimulated T cell proliferation. The murine fibrosarcoma Meth‐KDE cell line constitutively produced TGF‐β1. Meth‐KDE tumor‐bearing host (TBH) syngeneic splenic mφs suppressed autoantigen‐ and alloantigen‐stimulated normal host (NH) CD4+ T cell proliferation. Pretreatment with Meth‐KDE supernatants induced NH mφs to suppress T cell proliferation as much as TBH mφs. Anti‐TGF‐β1 antibody treatment reversed Meth‐KDE‐induced NH mφ‐mediated suppression. Recombinant TGF‐β1‐induced mφ‐mediated suppression was not blocked during inhibition of prostaglandin E2 (PGE2), nitric oxide (NO), or TGF‐β1 production. However, Meth‐KDE‐induced mφ‐mediated suppression was partly reduced when PGE2 production was inhibited. Pretreatment with tumor cell‐derived TGF‐β1, but not recombinant TGF‐β1, increased activated mφ PGE2 production. These results show that additional tumor‐derived molecules aid in TGF‐β1‐enhanced PGE2 production. Also, TGF‐β1 alone up‐regulates mφ synthesis of suppressor molecules that are different from PGE2, NO, and TGF‐β1. Although TGF‐β1 has direct suppressor activity on lymphocytes, these results show that release of tumor cell TGF‐β1 also induces mφ suppressor activity. J. Leukoc. Biol. 57: 919–928; 1995.