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Phenotypical and functional specialization of FOXP3+ regulatory T cells

Nature Reviews Immunology volume 11, pages 119–130 (2011)Cite this article

Subjects

Key Points

  • TReg cells 'walk the line' by preventing autoimmunity while allowing the formation of protective antipathogen and antitumour immune responses.

  • TReg cells can be divided, based on their expression of activation and homing receptors, into populations with distinct migratory, functional and homeostatic characteristics.

  • TReg cells accumulate within both lymphoid and non-lymphoid tissues, and the proper localization of TReg cells is critical to their ability to function and maintain immune homeostasis in vivo.

  • TReg cells use distinct molecular programmes to restrain TH1, TH2 and TH17 cell-mediated immune responses.

  • TReg cells can alter their phenotype and function in response to molecular cues such as cytokines and vitamin metabolites that are present in the immune environment.

  • The phenotypical and functional stability of TReg cells remains controversial, and different experimental systems have yielded conflicting results regarding the ability of TReg cells to convert to other pro-inflammatory T cell lineages.

Abstract

Forkhead box P3 (FOXP3)+ regulatory T (TReg) cells prevent autoimmune disease, maintain immune homeostasis and modulate immune responses during infection. To accomplish these tasks, TReg cell activity is precisely controlled, and this requires TReg cells to alter their migratory, functional and homeostatic properties in response to specific cues in the immune environment. We review progress in understanding the diversity of TReg cells, TReg cell function in different anatomical and inflammatory settings, and the influence of the immune environment on TReg cell activity. We also consider how these factors affect immune-mediated disease in the contexts of infection, autoimmunity, cancer and transplantation.

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Figure 1: Differing immunosuppressive mechanisms used by TReg cells in lymphoid and non-lymphoid tissues.
Figure 2: Functional differentiation of TReg cells and TH cells.
Figure 3: Modulation of TReg cell activity by different environmental factors.

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Acknowledgements

The authors would like to thank all past and present members of the Campbell lab for interesting discussions and intellectual input essential to this Review.

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Authors and Affiliations

  1. Immunology Program, Benaroya Research Institute, Seattle, 98103, Washington, USA

    Daniel J. Campbell

  2. Department of Immunology, University of Washington School of Medicine, Seattle, 98195-7650, Washington, USA

    Meghan A. Koch

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Correspondence to Daniel J. Campbell.

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Campbell, D., Koch, M. Phenotypical and functional specialization of FOXP3+ regulatory T cells. Nat Rev Immunol 11, 119–130 (2011). https://doi.org/10.1038/nri2916

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