Further checkpoints in Th1 development

Tight control of Th1 immunity is essential to prevent immunopathology. Central to control of the IFN-gamma gene is the transcription factor T-bet, whose induction is Stat-1 dependent. IL-12 is dominant in directing Th1 development, while synergizing with IL-18 for IFNgamma production from differentiated Th1 cells. In this issue of Immunity, IL-27 is described, which acts in synergy with IL-12 early in Th1 development from naive T cells via the receptor TCCR/WSX-1. We review the coordination of these checkpoints in Th1 development and function.