T Lymphocytes: Plasticity of Subsets

Abstract

The initial characterisation of both mouse and human T cells described distinct and sharply defined cytokine patterns that were relatively stable and were functionally specialised for successfully attacking different pathogens. Additional phenotypes were then described, extending the range of functional types. However, more recently there have been many reports of further changes in cytokine patterns, and it is clear that all the recognised phenotypes were more plastic than originally thought. In particular, many intermediates between established subsets have been reported, for example Th1/Th17 cells expressing both IFNγ (interferon‐gamma) and IL (interleukin)‐17. This plasticity provides extra versatility for the immune system to adapt to changing infections and to altered requirements in different locations. A model of stochastic differentiation is presented, to visualise potential differentiation modes in the framework of a landscape model and to try to encourage discussion and experimentation regarding different mechanisms for plasticity.

Key Concepts

  • Initial models of highly stable T‐cell subsets were useful but underestimated diversity.
  • Flexibility is overlaid on partial stability.
  • Many intermediate phenotypes can be induced.
  • Several questions remain regarding temporary versus long‐term plasticity alterations.
  • Models for visualising differentiation need to be modified to include flexibility around a theme.
  • Incorporation of stochastic trends may give a more useful representation of differentiation.

Keywords: T‐cell subset; stochastic variation; stability; plasticity; effector adaptation; intermediate T‐cell phenotypes

Figure 1. Plasticity of major recognised Th effector phenotypes. Transitions between different Th phenotypes are shown, concentrating on states leading to or deriving from Th1, Th2 and Th17 cells. Only transitions validated by experimental evidence are shown – the numbers in black circles indicate the reference number supporting each transition. Tfh and Th22 cells have been omitted from the diagram. The focus of the diagram is on transitions from the canonical phenotypes, (Th1, Th2, etc.) to intermediate forms, such as Th1/Th17. Although there is some evidence for complete conversion, for example Th1 to Th2, these experiments are normally less conclusive because T cells do not synthesise their entire cytokine repertoire in response to each stimulation. Numbers next to each transition in the figure refer to the following references: Sad and Mosmann , Sallusto et al., Divekar et al., Panzer et al., Hegazy et al., Wang et al., Xu et al., Brown et al., Annunziato et al.; Lee et al., Dardalhon et al., Veldhoen et al., Gagliani et al..
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Further Reading

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Bonelli M, Shih HY, Hirahara K, et al. (2014) Helper T cell plasticity: impact of extrinsic and intrinsic signals on transcriptomes and epigenomes. Current Topics in Microbiology and Immunology 381: 279–326.

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Perez‐Mazliah D and Langhorne J (2014) CD4 T‐cell subsets in malaria: TH1/TH2 revisited. Frontiers in Immunology 5: 671.

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Mosmann, Tim R, and Rebhahn, Jonathan A(Nov 2016) T Lymphocytes: Plasticity of Subsets. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0026253]