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

Publication ,  Journal Article
Grimm, EA; Crump, WL; Durett, A; Hester, JP; Lagoo-Deenadalayan, S; Owen-Schaub, LB
Published in: Cancer Immunol Immunother
1988

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.

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Published In

Cancer Immunol Immunother

DOI

ISSN

0340-7004

Publication Date

1988

Volume

27

Issue

1

Start / End Page

53 / 58

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factors
  • Platelet-Derived Growth Factor
  • Platelet Factor 4
  • Peptides
  • Neoplasm Proteins
  • Lymphokines
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Interleukin-2
 

Citation

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Grimm, E. A., Crump, W. L., Durett, A., Hester, J. P., Lagoo-Deenadalayan, S., & Owen-Schaub, L. B. (1988). TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity. Cancer Immunol Immunother, 27(1), 53–58. https://doi.org/10.1007/BF00205758
Grimm, E. A., W. L. Crump, A. Durett, J. P. Hester, S. Lagoo-Deenadalayan, and L. B. Owen-Schaub. “TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity.Cancer Immunol Immunother 27, no. 1 (1988): 53–58. https://doi.org/10.1007/BF00205758.
Grimm EA, Crump WL, Durett A, Hester JP, Lagoo-Deenadalayan S, Owen-Schaub LB. TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity. Cancer Immunol Immunother. 1988;27(1):53–8.
Grimm, E. A., et al. “TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity.Cancer Immunol Immunother, vol. 27, no. 1, 1988, pp. 53–58. Pubmed, doi:10.1007/BF00205758.
Grimm EA, Crump WL, Durett A, Hester JP, Lagoo-Deenadalayan S, Owen-Schaub LB. TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity. Cancer Immunol Immunother. 1988;27(1):53–58.
Journal cover image

Published In

Cancer Immunol Immunother

DOI

ISSN

0340-7004

Publication Date

1988

Volume

27

Issue

1

Start / End Page

53 / 58

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Transforming Growth Factors
  • Platelet-Derived Growth Factor
  • Platelet Factor 4
  • Peptides
  • Neoplasm Proteins
  • Lymphokines
  • Lymphocyte Activation
  • Killer Cells, Natural
  • Interleukin-2