Resveratrol attenuates stimulated T-cell activation and proliferation: potential therapy against cellular rejection in organ transplantation.

Abstract

Background: Pharmaceuticals to inhibit mammalian target of rapamycin (mTOR) protein, which plays an integral role in T cell survival and function, have been used to prevent complications associated with organ transplantation. Although studies have individually shown that resveratrol can inhibit mTOR and that inhibiting mTOR leads to attenuated immune function, no studies to date have examined these two functions conjointly under one study. Therefore, we hypothesize that resveratrol will decrease mTOR activation and expression as well as attenuate stimulated T cell activation and proliferation in peripheral blood mononuclear cells (PBMC).

Methods and materials: Human PBMC were isolated and cultured. The cells were pre-treated with resveratrol (50 μM) overnight (18 hrs) before stimulation. The cells were collected for subsequent biochemical analysis after 1, 3, and 5 days. Additionally, the cells were stained with proliferation dye and cultured for 24 hours in PMA/Ionomycin with resveratrol for flow cytometry analysis.

Results: Resveratrol treated stimulated PBMCs displayed a significant decrease in activated phosphorylation of mTOR at days 1, 3, and 5 (P < 0.0329). Markers of T cell activation, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (INF-γ), were also significantly reduced along with T cell proliferation following stimulated PBMC resveratrol treatment when compared to vehicle-treated controls (P < 0.01).

Conclusion: Taken together, our data suggest that resveratrol can decrease the immune response of stimulated T-cells and inhibit the expression and activation of mTOR mediated cellular signalling under the same study setting. Therefore, resveratrol proposes a possible adjunctive therapy option for patients undergoing organ transplantation.