Gliadin Activates HLA Class I-Restricted CD8+ T Cells in Celiac Disease Intestinal Mucosa and Induces the Enterocyte Apoptosis

Mazzarella, Giuseppe; Stefanile, Rosita; Camarca, Alessandra; Giliberti, Paolo; Cosentini, Elena; Marano, C; Iaquinto, Gaetano; Giardullo, Nicola; Auricchio, Salvatore; Sette, Alessandro; Troncone, Riccardo; Gianfrani, Carmen

doi:10.1053/j.gastro.2008.01.008

Cited by 87 publications

(69 citation statements)

References 36 publications

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“…Therefore, it is generally thought that IELs do not mediate tissue damage through gluten recognition. Nevertheless, one group has identified a class I gluten epitope recognized by CD8 + T cells isolated from CD intestinal mucosa (40). If the αEβ7 + CD38 + CD8 + T cells we describe are responding to gluten, this would imply a rapid and efficient cross-presentation of gluten on MHC class I. are seen in TCRβ clones using TRBV7-9 and TRBV7-8, respectively.…”

Section: Discussionmentioning

confidence: 82%

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Han

Newell

Glanville

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

181

146

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Celiac disease is an intestinal autoimmune disease driven by dietary gluten and gluten-specific CD4 + T-cell responses. In celiac patients on a gluten-free diet, exposure to gluten induces the appearance of gluten-specific CD4 + T cells with gut-homing potential in the peripheral blood. Here we show that gluten exposure also induces the appearance of activated, gut-homing CD8 + αβ and γδ T cells in the peripheral blood. Single-cell T-cell receptor sequence analysis indicates that both of these cell populations have highly focused Tcell receptor repertoires, indicating that their induction is antigendriven. These results reveal a previously unappreciated role of antigen in the induction of CD8 + αβ and γδ T cells in celiac disease and demonstrate a coordinated response by all three of the major types of T cells. More broadly, these responses may parallel adaptive immune responses to viral pathogens and other systemic autoimmune diseases.autoimmunity | mucosal immunity

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Section: Discussionmentioning

confidence: 82%

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Han

Newell

Glanville

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

181

146

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“…To evaluate the role of IL-17 in the induction of epithelial cell apoptosis and villous atrophy [28], we treated the epithelial cell line, CaCo-2, with IL-17 to study the induction of apoptosis. CaCo-2 cells showed expression of IL-17RA, and IL-17 potentiated the expression of the anti-apoptotic gene bcl-2.…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

Lahdenperä

Hölttä

Ruohtula

et al. 2012

Clinical and Experimental Immunology

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“…For example, gliadin is known to cause cellular cytoskeleton rearrangement, through the zonulin pathway, and loss of tight junctions, modifying protein expression, which results in a paracellular permeability increase of the small intestine mucosa [36][37][38][39][40][41]. Moreover, gliadin has a toxic effect because it reduces small intestinal mucosal cell F-actin content, inhibits RNA and DNA synthesis, inhibits epithelial cell growth, increases oxidative stress, and induces apoptosis, thereby altering mucosal homeostasis [42][43][44][45][46]. Alternatively, gluten might cause gastrointestinal neuromuscular abnormalities by increased acetylcholine release from the myenteric plexus and consequent cholinergic activation, as indicated by experimental models in DQ8-restricted mice.…”

Section: Pathogenesis Of CD Wa and Ncgsmentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: Literature Review

Mansueto

Seidita

D’Alcamo

et al. 2014

Journal of the American College of Nutrition

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Key words: non-celiac gluten sensitivity, celiac disease, wheat allergy, food allergy, HLA, flow cytometric basophil activation test, innate immune response Background: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS).Aim: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients.Methods: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS.Results: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.Conclusions: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points:• Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet.• NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy.• Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course.• A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.• Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup. Abbreviations: CD = celiac disease, WA = wheat allergy, NCGS = non-celiac gluten sensitivity, GFD = gluten-free diet, IBS = irritable bowel syndrome, HLA = human leukocyte antigen, tTg = antitissue transglutaminase, AGA = antigliadin antibodies, EMA = endomysial antigen, DGP = deami...

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Gliadin Activates HLA Class I-Restricted CD8+ T Cells in Celiac Disease Intestinal Mucosa and Induces the Enterocyte Apoptosis

Abstract: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.

Cited by 87 publications

References 36 publications

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

Non-Celiac Gluten Sensitivity: Literature Review

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Gliadin Activates HLA Class I-Restricted CD8+ T Cells in Celiac Disease Intestinal Mucosa and Induces the Enterocyte Apoptosis

Abstract: These data indicate that gliadins contain peptides able to activate, through a TCR/HLA class I interaction, CD8-mediated response in intestinal CD mucosa and to induce the enterocyte apoptosis.

Cited by 87 publications

References 36 publications

Dietary gluten triggers concomitant activation of CD4 + and CD8 + αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 + and CD8 + αβ T cells and γδ T cells in celiac disease

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes

Non-Celiac Gluten Sensitivity: Literature Review

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Product

Resources

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Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease

Dietary gluten triggers concomitant activation of CD4 ⁺ and CD8 ⁺ αβ T cells and γδ T cells in celiac disease