Effects of transforming growth factor beta (TGF-beta) on the lymphocyte- and cytokine-mediated destruction of islet cells in the BB/Wor rat

Abstract

The objective of this study was to determine whether transforming growth factor beta (TGF-beta) can inhibit the destruction of islet cells by either spleen cells from acutely diabetic BB/Wor rats, or by the cytokines tumor necrosis factor (TNF) and interferon gamma (IFN-gamma). It has previously been reported that effector spleen cells from diabetic BB/Wor rats and humans can specifically lyse islet cell targets in a 51Cr release assay; further evidence in BB rats suggests that these cells are natural killer (NK) cells. Similarly, TNF and IFN-gamma have been shown to act synergistically to destroy islet cell monolayers. TGF-beta inhibits NK cell generation and activity, and was shown to inhibit the production and/or activity of various cytokines. A 51Cr release assay was used to evaluate the effects of TGF-beta on both the lymphocyte- and cytokine-mediated destruction of islet cells. Results showed that TGF-beta specifically inhibits lymphocyte-mediated islet cell lysis at concentrations of 10 and 1 ng/ml. Preincubation of islets with TGF-beta for 24 h prior to the addition of 51Cr-labeled target cells markedly increased the percent inhibition of islet cell lysis. TGF-beta (10 ng/ml) was also shown to significantly inhibit the TNF and IFN-gamma-induced lysis of islet cell monolayers. These findings demonstrate that TGF-beta can significantly reduce both the diabetic spleen cell, and cytokine-mediated lysis of islet cells and suggest that it may play a role in preventing islet damage in vivo.