title: Induction of appropriate Th-cell phenotypes: cellular decision-making in heterogeneous environments.
abstract: 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.
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: H-J
authors.initials: HJ
authors.lastname: van den Ham
authors.affiliation: Department of Viroscience, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: A C
authors.initials: AC
authors.lastname: Andeweg
authors.affiliation: Theoretical Biology & Bioinformatics, Utrecht University, Utrecht, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: de Boer
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D016207:Cytokines / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005246:Feedback; D006801:Humans; D007113:Immunity, Innate; D008213:Lymphocyte Activation; D000069452:Pathogen-Associated Molecular Pattern Molecules / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D059467:Transcriptome
chemical_list: D016207:Cytokines; D000939:Epitopes; D000069452:Pathogen-Associated Molecular Pattern Molecules
keywords: T-helper cells; Th-cell phenotypes; modelling; stochasticity