Neurotrophins, including nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 (NT-3) are essential factors for the development of the nervous system. In this report, we demonstrate gene expression of neurotrophins and their receptors in T helper 1 (Th1) and T helper 2 (Th2) cells induced from naïve CD4+ CD45RB+ T cells of ovalbumin-specific DO11.10 T cell receptor transgenic mice. Interestingly, the TrkC gene, which encodes a high affinity receptor for NT-3, was expressed in Th2 cells, but not in Th1 and naïve CD4+ T cells. Expression of the TrkC gene was markedly augmented by addition of anti-IFN-gamma monoclonal antibody (mAb) into the culture, whereas it was blocked by anti-IL-4 mAb. Moreover, NT-3 synergistically enhanced anti-CD3 mAb-induced IL-4 production by Th2 cells, but did not affect IFN-gamma production by Th1 cells. These data suggest that NT-3, through its receptor TrkC, plays a critical role in regulating the Th1/Th2 balance.