Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1988;27(1):53-8.
doi: 10.1007/BF00205758.

TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity

E A Grimm  1 , W L Crump 3rd, A Durett, J P Hester, S Lagoo-Deenadalayan, L B Owen-Schaub
Affiliations

TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity

E A Grimm et al. Cancer Immunol Immunother. 1988.

Abstract

Employing serum-free media, human peripheral blood mononuclear cells, and purified recombinant interleukin-2 (IL-2), conditions were observed in which the development of IL-2-driven cytotoxic activity was suppressed. The cytotoxic activity of such IL-2-generated lymphokine activated killing (LAK) was tested against natural killer-resistant cultured tumor cells (Daudi, Raji, and a glioma). LAK generation was inhibited by addition of some normal sera, normal platelets, or some tumor cells. Because recent reports have indicated that transforming growth factor-beta (TGF-beta)-like factors are often secreted by tumors and the acidic alpha granules of platelets and can be present in sera, we tested the effect of purified human TGF-beta on the activation of LAK. Our results indicated that TGF-beta is very suppressive for LAK induction, and can completely prevent both the IL-2-driven proliferation and cytotoxicity at concentrations as low as 5 ng/ml. Titrations of IL-2 and of TGF-beta indicated that the suppression is dose-dependent and can be avoided by employing higher levels of IL-2. It was also found that the suppressive effect of TGF-beta can be overcome by washing suppressed cell populations and further culture in low levels of IL-2. Collectively, these data indicate that TGF-beta can be a potent inhibitor of LAK generation under standard activation conditions, but that this effect is regulated by the relative level of IL-2 and may be overcome and/or reversed in vitro.

PubMed Disclaimer

References

    1. Anzano MA, Roberts AB, Smit JM, Sporn MB, DeLaco JE. Sacroma growth factor from conditioned medium of virally transformed cells is composed of both type a and type b transforming growth factors. Proc Natl Acad Sci USA. 1983;80:6264. - PMC - PubMed
    1. Anzano MA, Roberts AB, DeLaco JE, Wakefield LM, Assoian RK, Roche NS, Smith JM, Lazarus JE, Sporn MB. Increased secretion of type beta transforming growth factor accompanies viral transformation of cells. Mol Cell Biol. 1985;5:242. - PMC - PubMed
    1. Assoian RK, Komoriya A, Meyers CA, Sporn MB. Transforming growth factor-beta in human platelets: identification of major storage site, purification, and characterization. J Biol Chem. 1983;258:7155. - PubMed
    1. Brooks WM, Netsky MG, Normansell DE, Horwitz DA. Depressed cell-mediated immunity in patients with primary intracranial tumors: Characterization of a humoral immunosuppressive factor. J Exp Med. 1972;136:1631. doi: 10.1084/jem.136.6.1631. - DOI - PMC - PubMed
    1. Childs CB, Proper JA, Tucker RF, Moses HL. Serum contains a platelet-derived transforming growth factor. Proc Natl Acad Sci USA. 1982;79:5312. - PMC - PubMed

MeSH terms

LinkOut - more resources