Transforming growth factor-beta 1 down-regulates expression of membrane-associated lymphotoxin and secretion of soluble lymphotoxin by human lymphokine-activated killer T cells in vitro.

Lymphokine-activated T killer lymphocytes (T-LAK) are important effector cells in various diseases of tissue destructive reactions. They require stimulation with various cytokines to proliferate and mature into function effector cells. We have examined the role of various endogenously and exogenously added cytokines, and tumor necrosis factor (TNF)/lymphotoxin (LT) receptors in this process in vitro. The present report is a continuation of these studies. We found that human T-LAK cells express membrane-associated LT (mLT) but not TNF, and secrete high amount of soluble LT (sLT) but low levels of TNF. When added to the initial cultures or immature T-LAK cells, transforming growth factor-beta 1 (TGF-beta 1) suppressed both mLT expression and sLT secretion by 30-40%. Coculture of mature T-LAK cells with TGF-beta 1 caused 35% down-regulation of both mLT expression and sLT secretion after 18 h of incubation. Kinetic experiments indicated reduction of LT mRNA synthesis could occur in as little as 1 h when cocultured with 5 ng/ml of TGF-beta 1. TGF-beta 1 also reduced mLT induced T-LAK cell cytolytic activity on L929 cells in vitro. It appears TGF-beta 1 can down-regulate LT mRNA syntheses, mLT expression, and sLT secretion of human T-LAK cells in vitro.