Induction of appropriate Th cell phenotypes: Cellular decision-making in heterogeneous environments

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.

2011 Parasite Immunology
van den Ham HJ, Andeweg AC, de Boer RJ