Helper T (Th)-cell differentiation 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-cell phenotype decision-making is crucial in mounting effective host responses. This review discusses the different Th-cell phenotypes that have been identified and how Th cells adopt a particular phenotype. The regulation of Th-cell phenotypes has been studied extensively using mathematical models, which have explored the role of regulatory mechanisms such as 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-cell phenotypes, these instructive mechanisms could be easily subverted by pathogens. We discuss that 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-cell phenotypes while terminating incorrect responses.

Modelling, Stochasticity, T-helper cells, Th-cell phenotypes
dx.doi.org/10.1111/pim.12053, hdl.handle.net/1765/41683
Parasite Immunology
Erasmus MC: University Medical Center Rotterdam

van den Ham, H.J, Andeweg, A.C, & de Boer, R.J. (2013). Induction of appropriate Th-cell phenotypes: Cellular decision-making in heterogeneous environments. Parasite Immunology (Vol. 35, pp. 318–330). doi:10.1111/pim.12053