Effect of environmental chemicals on the Th1/Th2 development and exacerbation of airway hyperresponsiveness

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In this study, we have investigated the mechanisms of environmental chemicals to disturb Th1/Th2 balance. Here we show that environmental chemicals reduce intracellular GSH levels and forced increase in GSH levels by N-acetyl-L-Cysteine attenuate the effect of environmental chemicals to disturb Th1/Th2 development from naive CD4+ T cells. Furthermore, using one of the notable pollutant, TBT, we show that Th1 clones were more susceptible than Th2 clones to the TBT-induced apoptosis as defined by Annexin V binding to phosphatidylserine residues. Flow cytometry showed that Th1 clones generated higher level of intracellular H_2O_2 in response to TBT treatment than Th2 clones. An inverse correlation between basal levels of intracellular GSH and TBT-induced increase in H_2O_2 generation was observed. These results suggest that TBT more easily induce Th1 apoptosis via generation of ROS, due to the low GSH level, and that TBT may contribute to the amplification of Th2-predominance. We presume that lower basal levels of GSH in Th1 cells are important factors that determine the susceptibility of Th1 cells to TBT induced apoptosis. Based on the data we have presented here and previously, we propose a novel mechanism by which the environmental pollutants contribute to the increased prevalence of allergic diseases by induction of Th2 predominance via selective induction of apoptosis in differentiated Th1 cells as well as modulation of Th1/Th2 differentiation from naive CD4+ T cells.