Children's immunology, what can we learn from animal studies (2): Modulation of systemic Th1/Th2 immune response in infant mice after prenatal exposure to low-level toluene and toll-like receptor (TLR) 2 ligand.

It has been reported that the newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the prenatal or suckling stage may contribute to susceptibility to environmental toxic chemical exposure. In the present study, to clarify the effect of low-level toluene exposure on immune functions during developmental stage, pregnant mice were exposed to 0, 5, and 50 ppm toluene from gestational day 14 to day 19 with or without stimulation by peptidoglycan (PGN) of a gram-positive bacterial cell wall component, a toll-like receptor (TLR) 2 ligand. We examined Th1/Th2 balance in the offspring's at 3 weeks old using ELISA and real-time RT-PCR methods. Exposure of mice to 50 ppm toluene enhanced total immunoglobulin (Ig) G2a (Th1-dependent) level in plasma. On the other hand, splenic expression of transcription factor T-bet (Th1-specific), GATA-3 (Th2-specific) and Foxp3 (gene marker for regulatory CD4+CD25+ T-cells) mRNAs was suppressed in these mice, but not in the combination of 5 or 50 ppm toluene with PGN. In addition, total IgG1 (Th2 dependent) level was suppressed in the combination of 5 or 50 ppm toluene with PGN. Our findings indicate that modulation of Th1- and Th2-responses may occur in low-level toluene exposure and/or combination with PGN stimulation in infant mice.