Key Points
-
γδ T-cell deficits are more often associated with defective immunoregulation than with a failure of immunity.
-
γδ T cells are disproportionately enriched in epithelia, and in certain strains of mice, γδ T-cell deficiency is associated with a spontaneous pathology that resembles human atopic dermatitis.
-
In terms of many of their features and properties, γδ T cells resemble other unconventional T cells, including subsets of αβ T cells. Defects in these cells also lead to dysregulation and immunopathology.
-
The regulation that is exerted by γδ T cells occurs at the effector stage in the tissues, rather than at the primary stage in the lymph nodes. Because of this, unconventional T-cell activity has potential importance for the amelioration of organ-specific autoimmune disease.
-
Immunoregulatory γδ T-cell subsets have several effector potentials, including the potential for cytolysis and chemokine secretion.
-
Immunoregulation by γδ T cells is under genetic control.
Abstract
For a T-cell subset to be classified as immunoregulatory, it might reasonably be predicted that in its absence, animals would experience pathological immune dysregulation. Moreover, reconstitution of the subset should restore normal immune regulation. So far, these criteria have been satisfied by only a few of the candidate regulatory T-cell subsets, but among them is the intraepithelial γδ T-cell receptor (TCR)+ subset of mouse skin. In this article, we look at immunoregulatory γδ T cells, and the growing evidence for tissue-associated immunoregulation mediated by both γδ T cells and αβ T cells.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Hayday, A. C. γδ cells: a right time and a right place for a conserved third way of protection. Annu. Rev. Immunol. 18, 975–1026 (2000).
Tonegawa, S. Somatic generation of antibody diversity. Nature 302, 575–581 (1983).
Shen, Y. et al. Adaptive immune response of Vγ2Vδ2+ T cells during mycobacterial infections. Science 295, 2255–2258 (2002).
King, D. P. et al. Protective response to pulmonary injury requires γδ T lymphocytes. J. Immunol. 162, 5033–5036 (1999).
Hiromatsu, K. et al. A protective role of γδ T cells in primary infection with Listeria monocytogenes in mice. J. Exp. Med. 175, 49–56 (1992).
Skeen, M. J. & Ziegler, H. K. Induction of murine peritoneal γδ T cells and their role in resistance to bacterial infection. J. Exp. Med. 178, 971–984 (1993).
Selin, L. K., Santolucito, P. A., Pinto, A. K., Szomolanyi-Tsuda, E. & Welsh, R. M. Innate immunity to viruses: control of vaccinia virus infection by γδ T cells. J. Immunol. 166, 6784–6794 (2001).
Langhorne, J., Mombaerts, P. & Tonegawa, S. αβ and γδ T cells in the immune response to the erythrocytic stages of malaria in mice. Int. Immunol. 7, 1005–1111 (1995).
Boismenu, R. & Havran, W. An innate view of γδ T cells. Curr. Opin. Immunol. 9, 57–63 (1997).
Tanaka, Y., Morita, C., Nieves, E., Brenner, M. B. & Bloom, B. R. Natural and synthetic non-peptide antigens recognized by human γδ T cells. Nature 375, 155–158 (1995).
Constant, P. et al. Stimulation of human γδ T cells by nonpeptidic mycobacterial ligands. Science 264, 267–270 (1994). The prototype paper introducing the concept of new, low-molecular-mass ligands for T cells.
Chien, Y. H., Jores, R. & Crowley, M. P. Recognition by γδ T cells. Annu. Rev. Immunol. 14, 511–532 (1996).
Crowley, M. P. et al. A population of murine γδ T cells that recognize an inducible MHC class Ib molecule. Science 287, 314–316 (2000). This study provides strong biochemical evidence for the recognition of thymus leukaemia antigen (TL)-type (class IB MHC) molecules by the γδ T-cell receptor.
Tsujimura, K. et al. The binding of thymus leukaemia (TL) antigen tetramers to normal intestinal intraepithelial lymphocytes and thymocytes. J. Immunol. 167, 759–764 (2001).
Janeway, C. A. et al. Specificity and function of cells bearing γδ T-cell receptors. Immunol. Today 9, 73–76 (1988).
Steele, C. R., Oppenheim, D. E. & Hayday, A. C. γδ T cells: non-classical ligands for non-classical cells. Curr. Biol. 10, R282–R285 (2000).
Groh, B., Steinle, A., Bauer, S. & Spies, T. Recognition of stress-induced MHC molecules by intestinal epithelial γδ T cells. Science 279, 1737–1740 (1998).
Wu, J., Groh, V. & Spies, T. T-cell antigen receptor engagement and specificity in the recognition of stress-inducible MHC class-I-related chains by human epithelial γδ T cells. J. Immunol. 169, 1236–1240 (2002).
Correa, I. et al. Most γδ T cells develop normally in β2-microglobulin-deficient mice. Proc. Natl Acad. Sci. USA 89, 653–657 (1992).
Das, G. & Janeway, C. A. Jr. Development of CD8αα and CD8αβ T cells in major histocompatibility complex class-I-deficient mice. J. Exp. Med. 190, 881–884 (1999).
Bucy, P., Chen, C. L., Cihak, J., Losch, U. & Cooper, M. Avian T cells expressing γδ receptors localize in the splenic sinusoids and the intestinal epithelium. J. Immunol. 141, 2200–2205 (1988).
Stingl, G. et al. Thy-1+ dendritic epidermal cells express T3 antigen and the T-cell receptor γ-chain. Proc. Natl Acad. Sci. USA 84, 4586–4590 (1987).
Asarnow, D. et al. Limited diversity of γδ antigen-receptor genes of Thy-1+ dendritic epidermal cells. Cell 55, 837–847 (1988). The prototype paper introducing the concept of a monomorphic T-cell repertoire associated with a specific tissue.
Goodman, T. & Lefrancois, L. Expression of the γδ T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 333, 855–858 (1988).
Kyes, S., Carew, E., Carding, S. R., Janeway, C. A. & Hayday, A. Diversity in T-cell receptor γ gene usage in intestinal epithelium. Proc. Natl Acad. Sci. USA 86, 5527–5531 (1989).
Itohara, S. et al. Homing of a γδ thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature 343, 754–757 (1990).
Hayday, A. & Viney, J. L. The ins and outs of body-surface immunology. Science 290, 97–100 (2000).
Allison, J. P. & Havran, W. L. The immunobiology of T cells with invariant γδ antigen receptors. Annu. Rev. Immunol. 9, 679–705 (1991).
Haas, W. γδ cells. Annu. Rev. Immunol. 11, 637–685 (1993).
Havran, W. L. & Allison, J. P. Developmentally ordered appearance of thymocytes expressing different T-cell antigen receptors. Nature 335, 443–445 (1988).
McVay, L. D., Jaswal, S. S., Kennedy, C., Hayday, A. & Carding, S. The generation of human γδ T-cell repertoires during fetal development. J. Immunol. 160, 5851–5860 (1998).
Lantz, O. & Bendelac, A. An invariant T-cell receptor α-chain is used by a unique subset of major histocompatibility complex class-I-specific CD4+ and CD4−8− T cells in mice and humans. J. Exp. Med. 180, 1097–1106 (1994).
Bendelac, A. Positive selection of mouse NK1.1+ T cells by CD1-expressing cortical thymocytes. J. Exp. Med. 182, 2091–2096 (1995).
Tilloy, F. et al. An invariant T-cell receptor α-chain defines a novel TAP-independent major histocompatibility complex class-Ib-restricted αβ T-cell subpopulation in mammals. J. Exp. Med. 189, 1907–1921 (1999).
Lefrancois, L. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J. Immunol. 147, 1746–1751 (1991).
Arstila, T. et al. Identical T-cell clones are located within the mouse gut epithelium and lamina propria and circulate in the thoracic duct lymph. J. Exp. Med. 191, 823–834 (2000).
Hayday, A., Theodoridis, E., Ramsburg, E. & Shires, J. Intraepithelial lymphocytes: exploring the Third Way in immunology. Nature Immunol. 2, 997–1003 (2001).
Havran, W., Chien, Y. & Allison, J. Recognition of self-antigens by skin-derived T cells with invariant γδ antigen receptors. Science 252, 1430–1432 (1991).
Girardi, M. et al. Regulation of cutaneous malignancy by γδ T cells. Science 294, 605–609 (2001).
Rocha, B., von Boehmer, H. & Guy-Grand, D. Selection of intraepithelial lymphocytes with CD8αα co-receptors by self-antigen in the murine gut. Proc. Natl Acad. Sci. USA 89, 5336–5340 (1992).
Lin, T. et al. Autospecific γδ thymocytes that escape negative selection find sanctuary in the intestine. J. Clin. Invest. 104, 1297–1305 (1999). An interesting paper providing evidence that gut-associated γδ T cells are positively selected in the thymus.
Urdahl, K. B., Sun, J. C. & Bevan, M. J. Positive selection of MHC class-Ib-restricted CD8+ T cells on hematopoietic cells. Nature Immunol. 3, 772–779 (2002).
Tsujimura, K. T. et al. Positive selection of γδ CTL by TL antigen expressed in the thymus. J. Exp. Med. 184, 2175–2184 (1996).
Mallick-Wood, C. A. et al. Conservation of T-cell receptor conformation in epidermal γδ cells with disrupted primary Vγ gene usage. Science 279, 1729–1733 (1998).
Ferrero, I., Wilson, A., Beermann, F., Held, W. & MacDonald, H. R. T-cell receptor specificity is critical for the development of epidermal γδ T cells. J. Exp. Med. 194, 1473–1483 (2001).
Waters, W. R. & Harp, J. A. Cryptosporidium parvum infection in T-cell receptor (TCR)-α and TCR-δ deficient mice. Infect. Immun. 64, 1854–1857 (1996).
Smith, A. & Hayday, A. An αβ T-cell-independent immunoprotective response toward gut coccidia is supported by γδ cells. Immunology 101, 325–332 (2000).
Born, W. et al. Immunoregulatory functions of γδ T cells. Adv. Immunol. 71, 77–144 (1999).
Mombaerts, P., Arnoldi, J., Russ, F., Tonegawa, S. & Kaufmann, S. H. Different roles of αβ and γδ T cells in immunity against an intracellular bacterial pathogen. Nature 365, 53–56 (1993).
Fu, Y. X. et al. Immune protection and control of inflammatory tissue necrosis by γδ T cells. J. Immunol. 153, 3101–3115 (1994).
D'Souza, C. D. et al. An anti-inflammatory role for γδ T cells in acquired immunity to Mycobacterium tuberculosis. J. Immunol. 158, 1217–1221 (1997). A good example of how defects in γδ T cells affect the form, but not the overall outcome, of the immune response that develops to a naturally administered pathogen.
Mukasa, A. et al. Bacterial infection of the testis leading to autoaggressive immunity triggers apparently opposed responses of αβ and γδ T cells. J. Immunol. 155, 2047–2056 (1995). A thorough paper showing that the defects in γδ T-cell-deficient mice are evident as overt inflammation, whereas the main consequence of a defect in αβ T cells is failure to control infection.
Mukasa, A., Born, W. & O'Brien, R. L. Inflammation alone evokes the response of a TCR-invariant mouse γδ T-cell subset. J. Immunol. 162, 4910–4913 (1999).
Peng, S., Madaio, M., Hayday, A. C. & Craft, J. Propagation and regulation of systemic autoimmunity by γδ T cells. J. Immunol. 157, 5689–5698 (1996).
Wen, L. et al. Immunoglobulin synthesis and generalised autoimmunity in mice congenitally deficient in αβ T cells. Nature 369, 654–658 (1994).
Horner, A. A., Jabara, H., Ramesh, N. & Geha, R. S. γδ T lymphocytes express CD40 ligand and induce isotype switching in B lymphocytes. J. Exp. Med. 181, 1239–1244 (1995).
Pao, W. et al. γδ T-cell help for B cells is stimulated by repeated parasitic infection. Curr. Biol. 6, 1317–1325 (1996).
King, D. P. et al. Cutting edge: protective response to pulmonary injury requires γδ T lymphocytes. J. Immunol. 162, 5033–5036 (1999).
Ladel, C. H., Blum, C. & Kaufmann, S. H. E. Control of natural killer cell-mediated innate resistance against the intracellular pathogen Listeria monocytogenes by γδ T lymphocytes. Infect. Immun. 64, 1744–1749 (1996).
Huber, S., Graveline, D., Newell, M., Born, W. & O'Brien, R. Vγ1+ T cells suppress and Vγ4+ T cells promote susceptibility to coxsackievirus B3-induced myocarditis in mice. J. Immunol. 165, 4174–4181 (2000). This study provides evidence that the outcome of immunoregulation by γδ T cells can be complex, with both pro- and anti-inflammatory consequences, depending on which γδ T-cell subsets are dominant.
Huber, S., Sartini, D. & Exley, M. Vγ4+ T cells promote autoimmune CD8+ cytolytic T-lymphocyte activation in coxsackievirus B3-induced myocarditis in mice: role for CD4+ TH1 cells. J. Virol. 76, 10785–10790 (2002).
Hoyne, G. F., Dallman, M. J. & Lamb, J. R. T-cell regulation of peripheral tolerance and immunity: the potential role for Notch signalling. Immunology 100, 281–288 (2000).
Smith, A. L. & Hayday, A. C. Genetic dissection of primary and secondary responses to a widespread natural pathogen of the gut, Eimeria vermiformis. Infect. Immun. 68, 6273–6280 (2000).
Roberts, S. et al. T-cell receptor αβ+ and γδ+ deficient mice display abnormal but distinct phenotypes toward a natural, widespread infection of the intestinal epithelium. Proc. Natl Acad. Sci. USA 93, 11774–11779 (1996).
Shiohara, T. et al. Loss of epidermal integrity by T-cell-mediated attack induces long-term local resistance to subsequent attack. I. Induction of resistance correlates with increases in Thy1+ epidermal-cell numbers. J. Exp. Med. 171, 1027–1041 (1990).
Shiohara, T., Moriya, N., Hayakawa, J., Itohara, S. & Ishikawa, H. Resistance to cutaneous graft-vs.-host disease is not induced in T-cell receptor δ gene-mutant mice. J. Exp. Med. 183, 1483–1489 (1996). This study implicates skin-associated γδ T cells in regulating infiltration into the epidermis of a line of autoreactive αβ T cells.
Girardi, M. et al. Resident skin-specific γδ T cells provide local, nonredundant regulation of cutaneous inflammation. J. Exp. Med. 195, 855–867 (2002). This study provides evidence that mice deficient for γδ T cells show a spontaneous loss of regulation of αβ T-cell responses in the skin.
Mihm, M. C., Soter, N. A., Dvorak, H. F. & Austen, J. F. The structure of normal skin and the morphology of atopic eczema. J. Invest. Dermatol. 67, 305–312 (1976).
Leung, D. Y. M., Bhan, A. K., Schneeberger, E. E. & Geha, R. S. Characterization of the mononuclear-cell infiltrate in atopic dermatitis using monoclonal antibodies. J. Allergy Clin. Immunol. 71, 47–56 (1983).
Chamlin, S. L. et al. Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity. J. Am. Acad. Dermatol. 47, 198–208 (2002).
Hanifin, J. M. & Raika, G. Diagnostic features of atopic dermatitis. Acta Dermatol. Venereol. (Stockholm) 92, 44–47 (1980).
Forrest, S. et al. Identifying genes predisposing to atopic eczema. J. Allergy Clin. Immunol. 104, 1066–1070 (1999).
Cookson, W. O. et al. Genetic linkage of childhood atopic dermatitis to psoriasis-susceptibility loci. Nature Genet. 27, 372–373 (2001).
Poussier, P., Ning, T., Banerjee, D. & Julius, M. A unique subset of self-specific intraintestinal T cells maintains gut integrity. J. Exp. Med. 195, 1491–1497 (2002). A clear demonstration that gut-associated unconventional αβ T cells downregulate systemic αβ T-cell-mediated inflammation in the tissues.
Gonzalez, A., Andre-Schmutz, I., Carnaud, C., Mathis, D. & Benoist, C. Damage control rather than unresponsiveness effected by protective Dx5+ T cells in autoimmune diabetes. Nature Immunol. 2, 1117–1125 (2001). An intriguing example of tissue-associated immune regulation of αβ T-cell responses by a subset of αβ T cells expressing a natural killer-cell marker.
Fahrer, A. et al. Attributes of γδ intraepithelial lymphocytes as suggested by their transcriptional profile. Proc. Natl Acad. Sci. USA 98, 10261–10266 (2001).
Shires, J., Theodoridis, E. & Hayday, A. Biological insights into TCRγδ+ and TCRαβ+ intraepithelial lymphocytes provided by serial analysis of gene expression (SAGE). Immunity 15, 419–434 (2001).
Bauer, S. et al. Activation of NK cells and T cells by NKG2d, a receptor for stress-inducible MICA. Science 285, 727–729 (1999).
Ogasawara, K. et al. Impairment of NK-cell function by NKG2D modulation in NOD mice. Immunity 18, 41–51 (2003).
Egan, P. & Carding, S. Downmodulation of the inflammatory response to bacterial infection by γδ T cells cytotoxic for activated macrophages. J. Exp. Med. 191, 2145–2158 (2000). A provocative mechanistic explanation for how γδ T cells might suppress the inflammatory response to a bacterial infection.
Vincent, M. S. et al. Apoptosis of Fashigh CD4+ synovial T cells by Borrelia-reactive Fas-ligandhigh γδ T cells in Lyme arthritis. J. Exp. Med. 184, 2109–2117 (1996).
Huber, S., Shi, C. & Budd, R. γδ T cells promote a TH1 response during coxsackievirus B3 infection in vivo: role of Fas and Fas ligand. J. Virol. 76, 6487–6494 (2002).
Huber, S., Graveline, D., Born, W. & O'Brien, R. Cytokine production by Vγ+-T-cell subsets is an important factor determining CD4+-TH-cell phenotype and susceptibility of BALB/c mice to coxsackievirus B3-induced myocarditis. J. Virol. 75, 5860–5869 (2001).
Wen, L. et al. Primary γδ-cell clones can be defined phenotypically and functionally as TH1/TH2 cells and illustrate the association of CD4 with TH2 differentiation. J. Immunol. 160, 1965–1974 (1998).
Yin, Z. et al. T-bet expression and failure of GATA-3 cross-regulation lead to default production of IFN-γ by γδ T cells. J. Immunol. 168, 1566–1571 (2002).
Zelenika, D. et al. The role of CD4+ T-cell subsets in determining transplantation rejection or tolerance. Immunol. Rev. 182, 164–179 (2001).
Young, J. D. et al. Thymosin β4 sulfoxide is an anti-inflammatory agent generated by monocytes in the presence of glucocorticoids. Nature Med. 5, 1424–1427 (1999).
Rudin, C. M., Engler, P. & Storb, U. Differential splicing of thymosin β4 mRNA. J. Immunol. 144, 4857–4862 (1990).
Jameson, J. et al. A role for skin γδ T cells in wound repair. Science 296, 747–749 (2002).
Komano, H. et al. Homeostatic regulation of intestinal epithelia by intraepithelial γδ T cells. Proc. Natl Acad. Sci. USA 92, 6147–6151 (1995).
Hampe, J. et al. Association between insertion mutation in NOD2 gene and Crohn's disease in German and British populations. Lancet 357, 1925–1928 (2001).
van Houten, N. & Huber, S. A. Genetics of coxsackie virus B3 (CVB3) myocarditis. Eur. Heart J. 12, 108–112 (1991).
Sugita, M. & Brenner, M. B. T-lymphocyte recognition of human group 1 CD1 molecules: implications for innate and acquired immunity. Semin. Immunol. 12, 511–516 (2000).
Jiang, H. & Chess, L. The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1. Annu. Rev. Immunol. 18, 185–216 (2000).
Sakaguchi, S., Fukuma, K., Kuribayashi, K. & Masuda, T. Organ-specific autoimmune diseases induced in mice by elimination of a T-cell subset. I. Evidence for the active participation of T cells in natural self-tolerance; deficit of a T-cell subset as a possible cause of autoimmune disease. J. Exp. Med. 161, 72–87 (1985).
Moore, T. A., Moore, B. B., Newstead, M. W. & Standiford, T. J. γδ T cells are critical for survival and early proinflammatory gene expression during murine Klebsiella pneumonia. J. Immunol. 165, 2643–2650 (2000).
Nam, J. L., Lewis, J., Girardi, M. & Tigelaar, R. E. Genetic analysis of spontaneous dermatitis in γδ T-cell-deficient mice. J. Invest. Dermatol. 119, 301 (2002).
Girardi, M. et al. Anti-inflammatory effects in the skin of thymosin-β4 splice-variants. Immunology (in the press).
Acknowledgements
We thank M. Girardi, our main collaborator in this work, and J. Lewis, J. Shires, M. Tigelaar and S. Creighton. We acknowledge support from the Wellcome Trust and the Yale Skin Diseases Research Center (National Institutes of Health).
Author information
Authors and Affiliations
Corresponding author
Glossary
- DENDRITIC EPIDERMAL T CELLS
-
(DETCs). γδ T-cell receptor (TCR)+ cells localized in the epidermis that are present in rodents and cattle, but not in humans. In mice, essentially all DETCs express precisely the same TCR, forming a prototype lymphocyte repertoire of limited diversity.
- MRL/LPR MICE
-
A strain of mice that spontaneously develop glomerular nephritis and other symptoms of systemic lupus erythematosus ('lupus'). The lpr mutation causes a defect in Fas, preventing the apoptosis of activated lymphocytes; the MRL strain contributes disease-associated mutations that have yet to be identified.
- MYOCARDITIS
-
An inflammatory disease of the heart that can be induced by various microbial and viral infections. The acute form of the disease seldom leads to lasting damage, but the chronic form can lead to fatal cardiomyopathy. A considerable part of the pathology seems to be a direct result of dysregulated activities of T helper 1 cells and CD8+ cytotoxic T lymphocytes.
- FVB/N
-
An inbred mouse strain that is increasingly favoured for analyses because of its vigorous reproductive performance and consistently large litters. Fertilized FVB/N eggs contain large and prominent pronuclei, which facilitates microinjection of DNA and efficient transgenesis.
- NON-OBESE DIABETIC
-
(NOD). A mouse strain that normally develops idiopathic autoimmune diabetes that closely resembles type 1 diabetes in humans. The target antigen(s) that is recognized by the pathogenic CD4+ T cells that initiate disease is expressed by pancreatic islet cells, but its identity has remained elusive.
- ATOPIC DERMATITIS
-
A chronic skin disease in which the skin becomes extremely itchy and inflamed, causing redness, swelling, cracking, weeping, crusting and scaling. Its multifactorial pathogenesis involves genetic susceptibility, environmental triggers and immune dysregulation (typically dominated by T helper 2 cells), with the involvement of immunoglobulin E contributing to its classification as an atopic disease.
- SEVERE COMBINED IMMUNODEFICIENCY
-
Mice of this phenotype lack functional T and B cells owing to a spontaneous mutation in the Prkdc gene (protein kinase, DNA activated, catalytic polypeptide) located on chromosome 16. These mice are often used for the reconstitution of T-cell subsets to study their functions in vivo in the absence of any other lymphocyte subsets.
- FAS LIGAND–FAS
-
A pair of ligand–receptor molecules of the tumour-necrosis factor (TNF)–TNF-receptor family, the engagement of which usually induces apoptosis of the FAS-expressing cell. So, this is a mode of cytolysis effected by FASL+ cells.
- ADOPTIVE TRANSFER
-
An experimental method in which lymphocytes from an antigen-primed donor mouse are introduced into a recipient mouse that lacks lymphocyte function.
- PSORIASIS
-
A chronic skin disease affecting 1–2% of the population, in which the skin becomes inflamed, producing red, thickened areas with silvery scales, most often on the scalp, elbows, knees and lower back. Recent evidence points to a T-cell-mediated pathogenesis in genetically susceptible individuals, resulting in inflammation and epidermal hyperplasia.
- CROHN DISEASE
-
Together with ulcerative colitis, Crohn disease is one of the two main forms of chronic inflammatory bowel disease (IBD). It most commonly affects the lower portion of the small intestine, resulting in symptoms of abdominal pain, diarrhoea, fever and weight loss. Analysis of the strong genetic predisposition led to the identification of mutations in the Nod2 gene that are particularly strongly associated with ileal disease, but not with ulcerative colitis.
Rights and permissions
About this article
Cite this article
Hayday, A., Tigelaar, R. Immunoregulation in the tissues by γδ T cells. Nat Rev Immunol 3, 233–242 (2003). https://doi.org/10.1038/nri1030
Issue Date:
DOI: https://doi.org/10.1038/nri1030
This article is cited by
-
γδ T cells: origin and fate, subsets, diseases and immunotherapy
Signal Transduction and Targeted Therapy (2023)
-
Changes in γδT Cells in Peripheral Blood of Patients with Ulcerative Colitis Exacerbations
Archivum Immunologiae et Therapiae Experimentalis (2021)
-
Butyrophilin-like proteins display combinatorial diversity in selecting and maintaining signature intraepithelial γδ T cell compartments
Nature Communications (2020)
-
Suppressive activity of Vδ2+ γδ T cells on αβ T cells is licensed by TCR signaling and correlates with signal strength
Cancer Immunology, Immunotherapy (2020)
-
New Insights into Asthma Inflammation: Focus on iNKT, MAIT, and γδT Cells
Clinical Reviews in Allergy & Immunology (2020)