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  • Review Article
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γδ T cells: functional plasticity and heterogeneity

Nature Reviews Immunology volume 2, pages 336–345 (2002)Cite this article

Key Points

  • γδ T cells are a unique and highly conserved lineage of T cells.

  • Differences in their tissue distribution and the types and mode of antigen recognition distinguish γδ T cells from αβ T cells.

  • The potential for γδ T-cell antigen receptor diversity and the number of unique antigen receptors that can be generated is greater than that of αβ T cells and B cells combined. This potential is, however, not realized.

  • γδ T cells are the first lineage of T cells to be generated; most populations are produced during fetal development.

  • Genetic and environmental factors operate to produce or select populations of γδ T cells that express antigen receptors encoded by specific gene segments. Human and mouse γδ T-cell repertoires are characterized by cells that express antigen receptors that are encoded by a single Vγ- and Vδ-gene segment

  • Increased numbers of γδ T cells have been described in a variety of infectious and autoimmune diseases.

  • In experimental animal models of inflammation, γδ T-cell involvement is staged; it occurs before and/or after αβ T-cell responses, coincident with or after the removal of the inflammatory stimulus. Functional analyses suggest that γδ T cells perform immunoregulatory functions that are complementary to the function of αβ T cells.

  • The functions that are carried out by γδ T cells change as the immune response progresses; different populations of γδ T cells, which are defined by differences in TCR Vγ–Vδ gene-segment usage, perform different functions during the early and later stages of pathogen-induced immune responses. The regulated and differential expression of γδ TCR co-receptors by target cells also serves to restrict and regulate γδ T-cell effector function.

  • Further insights into the biological function of γδ T cells will be provided by defining the populations of γδ T cells that are involved in a particular response and the conditions under which they are normally activated.

Abstract

γδ T cells remain an enigma. They are capable of generating more unique antigen receptors than αβ T cells and B cells combined, yet their repertoire of antigen receptors is dominated by specific subsets that recognize a limited number of antigens. A variety of sometimes conflicting effector functions have been ascribed to them, yet their biological function(s) remains unclear. On the basis of studies of γδ T cells in infectious and autoimmune diseases, we argue that γδ T cells perform different functions according to their tissue distribution, antigen-receptor structure and local microenvironment; we also discuss how and at what stage of the immune response they become activated.

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Figure 1: Organization of the mouse T-cell receptor γ- and δ-gene loci.
Figure 2: Mouse γδ T-cell generation is developmentally programmed.
Figure 3: γδ T cells contribute to different stages of inflammatory immune responses.

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Acknowledgements

We acknowledge the financial support of the National Institutes of Health and The Wellcome Trust. P.J.E. is supported by an Industry Research Fellowship from the National Health and Medical Research Council of Australia.

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Authors and Affiliations

  1. School of Biochemistry and Molecular Biology, The University of Leeds, Irene Manton Research Building, Room 8.91h, Leeds, LS2 9JT, West Yorkshire, UK

    Simon R. Carding

  2. Division of Autoimmunity and Transplantation, The Walter and Eliza Hall Institute of Medical Research, Victoria, 3050, Australia

    Paul J. Egan

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  1. Simon R. Carding
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Correspondence to Simon R. Carding.

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DATABASES

Entrez

HIV-1

Listeria monocytogenes

Mycobacterium tuberculosis

Sendai virus

LocusLink

β2-microglobulin

CD1

CD8

Fas

FasL

H60

HSP60

IL-4

IL-10

IFN-γ

KGF

MICA

MICB

TNF-α

OMIM

rheumatoid arthritis

type 1 diabetes

FURTHER INFORMATION

IMGT, ImMunoGeneTics database

Simon Carding's laboratory

Immunology at Leeds University

Glossary

OLIGOCLONALITY

A limited or small number of (T-cell) clones, as defined by the number of unique or individual antigen-receptor sequences identified in a population of cells.

T HELPER 1/T HELPER 2

(TH1/TH2). Subsets of CD4+ αβ T cells that are characterized by the cytokines they produce. TH1 T cells are generally involved in activating macrophages, whereas TH2 cells are involved in activating B cells.

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Carding, S., Egan, P. γδ T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2, 336–345 (2002). https://doi.org/10.1038/nri797

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