Signaling and Transcription in T Helper Development

The recognition of polarized T cell subsets defined by cytokine production was followed by a search to define the factors controlling this phenomenon. Suitable in vitro systems allowed the development of cytokine “recipes” that induced rapid polarization of naïve T cells into Th1 or Th2 populations. The next phase of work over the past several years has begun to define the intracellular processes set into motion during Th1/Th2 development, particularly by the strongly polarizing cytokines IL-12 and IL-4. Although somewhat incomplete, what has emerged is a richly detailed tapestry of signaling and transcription, controlling an important T cell developmental switch. In addition several new mediators of control have emerged, including IL-18, the intriguing Th2-selective T1/ST2 product, and heterogeneity in dendritic cells capable of directing cytokine-independent Th development.