Effects of fetal umbilical cord blood mesenchymal stem cells on γδT lymphocyte function and its related mechanism

Abstract

Objective To explore the effects of fetal umbilical cord blood mesenchymal stem cells on γδT lymphocyte function and its related mechanism. Methods The Human peripheral blood mononuclear cells (PBMCs) or γδT cells were activated and expanded with 2 μg/ml pamidronate and 100 IU/ml interleukin-2 (IL-2) with or without the presence Fetal umbilical cord blood mesenchymal stem cells (UCMSCs). Flow cytometry was performed to evaluate the effects of UC-MSCs on proliferation, cytokine expression and cytotoxicity of γδT cells; besides, flow cytometry was used to detect the effects of UC-MSCs on Fas-L and TRAIL expression in γδT cells and γδT cell apoptosis as well. Results UC-MSCs inhibited γδT cell proliferation in a dose-dependent but cell-contact independent manner; when PBMCs and UC-MSCs were cultured at a ratio of 3∶1 and 40∶1, IFN-γ+ cells decreased by 46.7% and 31.4%, respectively (P=0.001, P=0.021), granzyme B positive cells increased by 79.7%, 165%, respectively, while the ratio of TNF-α and IL-10 positive cells did not change significantly compared with the control group (P=0.062); Cytotoxicity test results showed that, UCMSCs inhibited the cytotoxicity ofγδT cells against influenza virus H1N1 infected A549 cells, and when PBMCs and UC-MSCs were cultured at a ratio of 3∶1 and 40∶1, Fas-L+ γδT cells decreased by 87.6% and 37.5% (P=0.000, 0.009), the proportion of TRIAL+ γδT cells decreased by 43.2% and 18.7% (P=0.037, 0.042), however, UC-MSCs did not affect γδ T cell apoptosis (P=0.070, 0.064). Conclusion UC-MSCs can suppress γδT cells proliferation and cytotoxicity and modulated their cytokine production, and Fas-L and TRAIL were involved in the regulation. Key words: Umbilical cord blood mesenchymal stem cells; γ δ T cells; Proliferation; Cytokines; Apoptosis