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. 1988 Aug;27(1):53–58. doi: 10.1007/BF00205758

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

Elizabeth A Grimm 1,2,✉, William L Crump III 1, April Durett 4, Jeane P Hester 4, Sandhya Lagoo-Deenadalayan 1, Laurie B Owen-Schaub 1
PMCID: PMC11037989  PMID: 3260821

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.

Keywords: Peripheral Blood Mononuclear Cell, Cytotoxic Activity, Suppressive Effect, Relative Level, Human Peripheral Blood

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