Induction of appropriate Th‐cell phenotypes: cellular decision‐making in heterogeneous environments

Summary 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‐ce...

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Bibliographic Details
Published in:Parasite immunology 2013-11, Vol.35 (11), p.318-330
Main Authors: Ham, H.‐J., Andeweg, A. C., Boer, R. J.
Format: Article
Language:English
Subjects:
Adaptive Immunity
Animals
Cytokines - immunology
Epitopes - immunology
Feedback
Humans
Immunity, Innate
Lymphocyte Activation
modelling
Pathogen-Associated Molecular Pattern Molecules - immunology
stochasticity
T-Lymphocytes, Helper-Inducer - cytology
T-Lymphocytes, Helper-Inducer - immunology
T-Lymphocytes, Regulatory - immunology
Th‐cell phenotypes
Transcriptome
T‐helper cells
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Summary:Summary 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.
ISSN:0141-9838
1365-3024
DOI:10.1111/pim.12053