Helper T cell differentiation (Th) is a key event in the development of the adaptive immune response. By the production of a range of cytokines, Th cells determine the type of immune response that is raised against an invading pathogen. Th cells can adopt many different phenotypes and Th phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms like autocrine cytokine signalling and cross-inhibition between self-activating transcription factors. At the single cell level, Th responses tend to be heterogeneous, but corrections can be made soon after T cell activation. Although pathogens and the innate immune system provide signals that direct the induction of Th phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss a model of success-driven feedback would select the most appropriate phenotype for clearing a pathogen. Given the heterogeneity in the induction phase of the Th response, such a success-driven feedback loop would allow the selection of effective Th phenotypes while terminating incorrect responses. This article is protected by copyright. All rights reserved.
|van den Ham HJ, Andeweg AC, de Boer RJ