Gamma-Delta T Lymphocytes in the Diagnostic Approach of Coeliac Disease

Nijeboer, Petula; Gils, Tom van; Reijm, Martine; Ooijevaar, Rogier E.; Lissenberg‐Witte, Birgit I.; Bontkes, Hetty J.; Mulder, Chris J.; Bouma, Gerd

doi:10.1097/mcg.0000000000001060

Cited by 26 publications

(37 citation statements)

References 29 publications

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“…Nevertheless, potential CD shows a percentage of TCRγδ + T cells that is significantly higher compared to healthy mucosa, consistently with previous studies ( p < 0.04) (Fig. A and B) . The increased infiltration of T cells in the gut mucosa of children with villous atrophy was also confirmed by the high percentage of TCRαβ + cells, most likely due to the inflammatory status induced by gluten ingestion ( p < 0.02, overt‐CD vs. controls) (Fig.…”

Section: Resultssupporting

confidence: 90%

The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease

et al. 2019

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Celiac disease (CD) is characterized by a spectrum of intestinal inflammatory lesions.Most patients have villous atrophy (overt-CD), while others have a morphologically normal mucosa, despite the presence of CD-specific autoantibodies (potential-CD). As the mechanism responsible for villous atrophy is not completely elucidated, we investigated biomarkers specific for the different celiac lesions. Phenotype and cytokine production of intestinal mucosa cells were analyzed by flow cytometry in gut biopsies of children with overt-or potential-CD and in healthy controls. Density of TCRγδ + T cells was found markedly enhanced in intestinal mucosa of children with overt-CD compared to potential-CD or controls. By contrast, very few IL4 + T cells infiltrated the mucosa with villous atrophy compared to morphologically normal mucosa. IL4 + T cells were classical CD4 + T-helper cells (CD161 − ), producing or not IFN-γ, and negative for IL17A. Our study demonstrated that the transition to villous atrophy in CD patients is characterized by increased density of TCRγδ + T cells, and concomitant disappearance of IL4 + cells. These findings suggest that immunomodulatory mechanisms are active in potential-CD to counteract the inflammatory cascade responsible of villous atrophy. Further studies are required to validate the use of IL4 + and TCRγδ + T cells as biomarkers of the different CD forms.Keywords: Celiac disease r Cytokines r Flow cytometry r Intestinal TCRγδ + T cells r Mucosal immunology Additional supporting information may be found online in the Supporting Information section at the end of the article.

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Section: Resultssupporting

confidence: 90%

The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease

et al. 2019

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“…It has been proposed that improved understanding of the true nature of the CD lesion could be deduced by 3-D printing and computerized modeling of the tissue ( 50 ). In recent times, robust flow cytometry methodology and quantification of gamma/delta (γδ) T cells have been proposed as complementary methods for aiding CD diagnosis and monitoring, particularly helpful in resolution of more difficult clinical cases ( 51 , 52 ). Analysis of an increase in γδ + T cells with a decrease in CD3 − IEL, the so-called “coeliac lymphogram,” was also shown to be useful in diagnosing seronegative CD cases ( 53 ).…”

Section: The Histological Lesion In CDmentioning

confidence: 99%

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

et al. 2020

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Coeliac disease is a common small bowel enteropathy arising in genetically predisposed individuals and caused by ingestion of gluten in the diet. Great advances have been made in understanding the role of the adaptive immune system in response to gluten peptides. Despite detailed knowledge of these adaptive immune mechanisms, the complete series of pathogenic events responsible for development of the tissue lesion remains less certain. This review contributes to the field by discussing additional mechanisms which may also contribute to pathogenesis. These include the production of cytokines such as interleukin-15 by intestinal epithelial cells and local antigen presenting cells as a pivotal event in the disease process. A subset of unconventional T cells called gamma/delta T cells are also persistently expanded in the coeliac disease (CD) small intestinal epithelium and recent analysis has shown that these cells contribute to pathogenic inflammation. Other unconventional T cell subsets may play a local immunoregulatory role and require further study. It has also been suggested that, in addition to activation of pathogenic T helper cells by gluten peptides, other peptides may directly interact with the intestinal mucosa, further contributing to the disease process. We also discuss how myofibroblasts, a major source of tissue transglutaminase and metalloproteases, may play a key role in intestinal tissue remodeling. Contribution of each of these factors to pathogenesis is discussed to enhance our view of this complex disorder and to contribute to a wider understanding of chronic immune-mediated disease.

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“…[96][97][98][99] Also, increased numbers of intraepithelial γδ T cells have been suggested as a biomarker for the diagnosis of coeliac disease when histology is inconclusive. 98,100 However, in a mouse model of food allergy, the allergic sensitisation induced by co-administration of cholera toxin and peanut antigens was followed by a decrease of number and proportion of γδ T cells in the intestine. 11 In the same study, the functional depletion of γδ T cells, through co-administration of antiγδ TCR blocking antibody during the sensitisation, led to a higher production of Th2 cytokines and peanut-specific IgE.…”

Section: Food Allergensmentioning

confidence: 99%

Hypersensitivities following allergen antigen recognition by unconventional T cells

Moreira

Souter

Chen

et al. 2020

Allergy

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Conventional T cells recognise protein-derived antigens in the context of major histocompatibility complex (MHC) class Ia and class II molecules and provide anti-microbial and anti-tumour immunity. Conventional T cells have also been implicated in type IV (also termed delayed-type or T cell-mediated) hypersensitivity reactions in response to protein-derived allergen antigens. In addition to conventional T cells, subsets of unconventional T cells exist, which recognise non-protein antigens in the context of monomorphic MHC class I-like molecules. These include T cells that are restricted to the cluster of differentiation 1 (CD1) family members, known as CD1restricted T cells, and mucosal-associated invariant T cells (MAIT cells) that are restricted to the MHC-related protein 1 (MR1). Compared with conventional T cells, much less is known about the immune functions of unconventional T cells and their role in hypersensitivities. Here, we review allergen antigen presentation by MHC-Ilike molecules, their recognition by unconventional T cells, and the potential role of unconventional T cells in hypersensitivities. We also speculate on possible scenarios of allergen antigen presentation by MHC-I-like molecules to unconventional T cells, the hallmarks of such responses, and the expected frequencies of hypersensitivities within the human population.

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Gamma-Delta T Lymphocytes in the Diagnostic Approach of Coeliac Disease

Abstract: A percentage of ≥14% CD3TCRγδ IEL has a high specificity for CD diagnosis and can be of diagnostic help in cases where diagnosis is not straightforward.

Cited by 26 publications

References 29 publications

The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease

The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

Hypersensitivities following allergen antigen recognition by unconventional T cells

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Gamma-Delta T Lymphocytes in the Diagnostic Approach of Coeliac Disease

Abstract: A percentage of ≥14% CD3TCRγδ IEL has a high specificity for CD diagnosis and can be of diagnostic help in cases where diagnosis is not straightforward.

Cited by 26 publications

References 29 publications

The intestinal expansion of TCRγδ+ and disappearance of IL4+ T cells suggest their involvement in the evolution from potential to overt celiac disease

The intestinal expansion of TCRγδ+ and disappearance of IL4+ T cells suggest their involvement in the evolution from potential to overt celiac disease

Coeliac Disease Pathogenesis: The Uncertainties of a Well-Known Immune Mediated Disorder

Hypersensitivities following allergen antigen recognition by unconventional T cells

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The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease

The intestinal expansion of TCRγδ⁺ and disappearance of IL4⁺ T cells suggest their involvement in the evolution from potential to overt celiac disease