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The functional plasticity of T cell subsets

Nature Reviews Immunology volume 9, pages 811–816 (2009)Cite this article

Abstract

In 1986, Robert Coffman and Timothy Mossman first described the division of CD4+ T cells into functional subsets, termed T helper 1 (TH1) and TH2, based on cytokine production, and in doing so unwittingly opened a Pandora's box of complexity and controversy. Although the mechanisms that regulate TH1 and TH2 cells are now well known, recent descriptions of other CD4+ T cell subsets — such as regulatory T cells, T follicular helper cells, TH17, TH22 and most recently TH9 and TH22 cells — have questioned how we think of T cell subsets and what commitment to a functional T cell subset means. Here, Nature Reviews Immunology asks four leaders in the field their thoughts on the functional plasticity of T cell subsets.

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Acknowledgements

J.B. would like to thank S. Bailey-Bucktrout, L. Jeker and X. Zhou for their hard work and thoughtful comments, M. Anderson, R. Locksley and A. Abbas for critical reading of this piece and the US National Institute of Health, Juvenile Diabetes Research Foundation, and University of California, San Francisco Diabetes Center for financial support.

C.R.M.'s views in this article are derived from work and discussions with D. Yu, C. Vinuesa and C. King. Charles Mackay is supported by the National Health and Medical Research Council of Australia.

J.J.O'S. would like to thank A. Laurence, L. Wei, V. Sartorelli, M. Gadina, R. Siegel and Y.e Belkaid for their lively discussion of this issue; however, I also wish to apologize to the members of my laboratory for taking so much time in lab meetings and journal clubs for endlessly debating this topic.

Author information

Authors and Affiliations

  1. San Francisco Diabetes Center and Department of Medicine, Jeffrey A. Bluestone is at the University of California, University of California, San Francisco 513 Parnassus Avenue, Box 0540–HSW 1114, San Francisco, California 94143, USA. jbluest@diabetes.ucsf.edu,

    Jeffrey A. Bluestone

  2. Charles R. Mackay is at Monash University, Faculty of Medicine, Nursing and Health Services, Clayton, Victoria, VIC 3800, Australia, and the Garvan Institute for Medical Research and St Vincent's Clinical School, University of New South Wales, Sydney, New South Wales, NSW 2010, Australia. charles.mackay@med.monash.edu.au,

    Charles R. Mackay

  3. John J. O'Shea is at the Molecular Immunology and Inflammation Branch, National Institutes of Arthritis and Musculoskeletal and Skin Diseases, US National Insitutes of Health, Bethesda, Maryland 20892, USA. osheaj@arb.niams.nih.gov,

    John J. O'Shea

  4. Brigitta Stockinger is at the Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK. bstocki@nimr.mrc.ac.uk,

    Brigitta Stockinger

Authors
  1. Jeffrey A. Bluestone
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CD4+ T cell diversity

Glossary

γδ T cells

T cells that express the γδ T cell receptor. These T cells are present in the skin, vagina and intestinal epithelium as intraepithelial lymphocytes. Although the exact function of these T cells is unknown, it has been suggested that mucosal γδ T cells are involved in innate immune responses.

Asymmetrical cell division

A type of division that produces two daughter cells with different properties. This is in contrast to normal cell division, which give rise to equivalent daughter cells. Notably, stem cells can divide asymmetrically to give rise to two distinct daughter cells: one copy of themselves and one cell programmed to differentiate into another cell type.

Class switching

The switch from expressing IgM to expressing other isotypes such as IgG, IgA or IgE that some B cells make after recognizing their cognate antigen. The decision of which isotype is generated is strongly influenced by the specific cytokine milieu and other cells such as T helper cells.

Germinal centre

A highly specialized and dynamic microenvironment that gives rise to secondary B cell follicles during an immune response. It is the main site of B cell maturation, leading to the generation of memory B cells and plasma cells, which produce high-affinity antibody.

Lymphoid-tissue inducer cell

A cell that is present in developing lymph nodes, Peyer's patches and nasopharynx-associated lymphoid tissue (NALT) and is required for the development of these lymphoid organs.

Lymphopenic mice

Mice that have lost both B and T cells, for example severe combined immunodeficiency mice or recombination activation gene-deficient mice, which lack an enzyme required for the generation of T and B cell receptors, or a loss of T cells only, as seen in nu/nu mice, which lack a thymus. T cell lymphopenia can be induced in mice by thymectomy on day three of life.

MicroRNAs

Small RNA molecules that regulate the expression of genes by binding to the 3′-untranslated regions of specific mRNAs.

Non-obese diabetic (NOD) mice

NOD mice spontaneously develop type 1 diabetes mellitus as a result of autoreactive T cell-mediated destruction of pancreatic β-islet cells.

Peyer's patches

Collections of lymphoid tissue located in the mucosa of the small intestine, with an outer epithelium layer consisting of specialized epithelial cells called M cells.

Systemic lupus erythematosus

(SLE). An autoimmune disease in which autoantibodies that are specific for DNA, RNA or proteins associated with nucleic acids form immune complexes that damage small blood vessels, particularly in the kidney. Patients with SLE generally have abnormal B and T cell function.

T follicular helper (TFH) cell

A CD4+ T cell that provides help to B cells in follicles and germinal centres. The TFH cell signature includes the expression of CXCR5, ICOS, CD40 ligand and IL-21, factors that mediate TFH cell homing to follicles and B cell help.

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Bluestone, J., Mackay, C., O'Shea, J. et al. The functional plasticity of T cell subsets. Nat Rev Immunol 9, 811–816 (2009). https://doi.org/10.1038/nri2654

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