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Induction of macrophage suppressor activity by fibrosarcoma‐derived transforming growth factor‐β1: contrasting effects on resting and activated macrophages
Author(s) -
Alieva David G.,
Walker Thomas M.,
Elgert Klaus D.
Publication year - 1995
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.57.6.919
Subject(s) - fibrosarcoma , transforming growth factor beta , tgf beta 1 , biology , transforming growth factor , prostaglandin e2 , t cell , ht1080 , beta (programming language) , cell growth , macrophage , cell culture , immune system , microbiology and biotechnology , cancer research , endocrinology , immunology , in vitro , biochemistry , genetics , computer science , programming language
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 E 2 (PGE 2 ), nitric oxide (NO), or TGF‐β1 production. However, Meth‐KDE‐induced mφ‐mediated suppression was partly reduced when PGE 2 production was inhibited. Pretreatment with tumor cell‐derived TGF‐β1, but not recombinant TGF‐β1, increased activated mφ PGE 2 production. These results show that additional tumor‐derived molecules aid in TGF‐β1‐enhanced PGE 2 production. Also, TGF‐β1 alone up‐regulates mφ synthesis of suppressor molecules that are different from PGE 2 , 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.