Fate vs choice: the immune system reloaded.

Development can occur by either instructive or stochastic processes. My colleagues and I have studied the contributions of these processes to differentiation of naïve CD4+ T-cells to either a Th1 or Th2 phenotype. Our initial discovery that pathogens in our in vitro priming system led to the development of Th1 cells through the action of interleukin-12 was important evidence of a link between innate and adaptive immunity. Subsequent studies in our laboratory revealed an important role for GATA-3 autoactivation in Th2 development. Other interesting projects that have emerged as a result of our Th cell differentiation studies include understanding the role of the inhibitory immunoreceptor B- and T-lymphocyte attenuator in the immune response, as well as the role of the transcription factor ERM in both T-cells and spermatogenesis. We currently maintain our interests in the Th differentiation field by trying to understand the role of type 1 interferons in Th1 development and the role of alternate promoters for the GATA-3 gene, among other things, but are also actively embarking on studies related to the choice between divergent cell types during embryonic stem cell differentiation.