Transforming growth factor-beta 1 (TGF-beta 1) and recombinant human tumor necrosis factor-alpha reciprocally regulate the generation of lymphokine-activated killer cell activity. Comparison between natural porcine platelet-derived TGF-beta 1 and TGF-beta 2, and recombinant human TGF-beta 1
Espevik, T.; Figari, I.S.; Ranges, G.E.; Palladino, M.A.
Journal of Immunology 140(7): 2312-2316
1988
ISSN/ISBN: 0022-1767 PMID: 3280680 Document Number: 321258
We have investigated the ability of porcine-platelet-derived transforming growth factor-.beta.1 (TGF-.beta.1) to inhibit the generation of lymphokine-activated killer (LAK) cells by human rIL-2. The results demonstrate that TGF-.beta.1, in a dose-related manner, significantly inhibits rIL-2-induced LAK cell activity against Daudi and COLO target cells and, to a lesser degree, against K-562 cells. Maximal inhibition was obtained by the addition of TGF-.beta.1 at the time of culture initiation and, to a lesser degree, on day 1. Only minimal inhibition was obtained when TGF-.beta.1 addition was delayed until day 2 of culture or when added directly into the LAK cell assay. Additional studies demonstrated that porcine platelet-derived TGF-.beta.2 and human rTGF-.beta.1 inhibited LAK cell generation similar to that obtained with TGF-.beta.1. The inhibition of LAK cell activity by TGF-.beta.1 was reversed by the addition of human rTNF-.alpha. at the initiation of culture. In addition, rTNF-.alpha. synergized with suboptimal levels of rIL-2 in the generation of LAK activity. After stimulation with rIL-2. LAK cells produced significant levels of IFN-.gamma., TNF-.alpha., and TNF-.beta. TGF-.beta.1 inhibited the production of these cytokines in a dose-related manner. The results extend the previous known activities for human rTNF-.alpha. and TGF-.beta.1 and further demonstrate the reciprocal relationship between these two molecules in the regulation of certain immune functions.