Definition of the initial immunologic modifications upon in vitro gliadin challenge in the small intestine of celiac patients

Maiuri, Luigi; Picarelli, Antonio; Boirivant, Monica; Coletta, S; Mazzilli, M. C.; Vincenzi, Massimo De; Londei, Marco; Auricchio, Salvatore

doi:10.1053/gast.1996.v110.pm8613040

Cited by 153 publications

(113 citation statements)

References 20 publications

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“…For instance, the small intestinal epithelial changes seen in untreated CD are mimicked by cytokines produced by gliadinactivated TCC [29,30]. However, many observations remain unexplained and the rapid small intestinal changes seen after gliadin challenge are probably not induced by gliadin specific T cells [5,31,32]. The role of the TCRg/d receptor cells [33] are still an enigma; their intraepithelial infiltration is disease specific, but the specificity is unknown.…”

Section: Discussionmentioning

confidence: 99%

“…Specific activation of mucosal T lymphocytes by wheat gliadin proteins is pivotal in the establishment of the small intestinal pathology [4][5][6]. The similarities between gut damage in CD and different model systems of intestinal cell-mediated immunity (intestinal graft-versus-host disease, transplantation of intestinal allografts and studies of T cell activation in fetal human small intestine) support the concept that T cell mediated mechanisms are of pathogenic importance in CD [7].…”

Section: Introductionmentioning

confidence: 99%

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Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Kett²,

et al. 1997

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The authors have analysed gliadin specific, CD4+ T cells isolated from small intestinal biopsies of 23 adult coeliac disease patients (20 on a gluten-free diet and three untreated) and nine control patients. The biopsies were stimulated ex vivo with a peptic/tryptic digest of gliadin for 24 h, and activated T cells were positively selected with paramagnetic beads coated with an antibody against the interleukin-2 receptor. The T cells were expanded and tested for gliadin reactivity and HLA restriction. Gliadin specific, polyclonal T cell lines were recovered from biopsies of all 23 patients. Inhibition studies of T cell lines from 21 patients with anti-HLA monoclonal antibodies indicated predominant presentation of the gliadin antigen by HLA-DQ2 in T cell lines from 11 patients (lines from seven patients with complete MoAb inhibition, the remaining with incomplete inhibition) and incomplete inhibition by HLA-DR3 in lines from three patients. Nine gliadin specific T cell clones from six patients were established; all of these were HLA-DQ2 restricted. Gliadin specific T cells were not found in biopsies from the non-coeliac controls. Our findings demonstrate that gliadin reactive T cells are commonly found in the intestinal mucosa of CD patients and they support the notion that the majority of T cells recognize gliadin peptide(s) when presented by the disease associated DQ2 molecules.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Gliadin Specific, HLA DQ2‐Restricted T Cells are Commonly Found in Small Intestinal Biopsies from Coeliac Disease Patients, but not from Controls

Kett²,

et al. 1997

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“…More recently, we demonstrated that ϳ20% of type 1 diabetic children react to rectal instillation of gliadin with a significant increment of lamina propria and epithelium CD3 ϩ and ␥␦ ϩ cells (14). The aims of this study were as follows: to look for signs of inflammation in the small intestinal mucosa of type 1 diabetic patients who did not show serological signs of CD, to look for immunohistochemical evidence of activated mucosal cell-mediated immunity, and to investigate the in vitro intestinal immune response to gliadin using an established organ culture system (15).…”

mentioning

confidence: 99%

In Vitro–Deranged Intestinal Immune Response to Gliadin in Type 1 Diabetes

Auricchio¹,

Paparo²,

Maglio³

et al. 2004

Diabetes

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Dietary gluten has been associated with an increased risk of type 1 diabetes. We have evaluated inflammation and the mucosal immune response to gliadin in the jejunum of patients with type 1 diabetes. Small intestinal biopsies from 17 children with type 1 diabetes without serological markers of celiac disease and from 50 age-matched control subjects were examined by immunohistochemistry. In addition, biopsies from 12 type 1 diabetic patients and 8 control subjects were cultured with gliadin or ovalbumin peptic-tryptic digest and examined for epithelial infiltration and lamina propria T-cell activation. The density of intraepithelial CD3 ؉ and ␥␦ ؉ cells and of lamina propria CD25 ؉ mononuclear cells was higher in jejunal biopsies from type 1 diabetic patients versus control subjects. In the patients' biopsies cultured with peptic-tryptic gliadin, there was epithelial infiltration by CD3 ؉ cells, a significant increase in lamina propria CD25 ؉ and CD80 ؉ cells and enhanced expression of lamina propria CD54 and crypt HLA-DR. No such phenomena were observed in control subjects, even those with celiac disease-associated HLA haplotypes. In conclusion, signs of mucosal inflammation were present in jejunal biopsies from type 1 diabetic patients, and organ culture studies indicate a deranged mucosal immune response to gliadin.

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“…Importantly, it has been possible to demonstrate that rapid and diseasespecific changes were observed in small intestine organ culture of CD patients with signs of local T-cell activation in organ cultures of celiac patients. 21,22 Although the four key factors (HLA alleles, triggering antigen, presence of infiltrating reactive T cells and a ready availability of tissue) to perform a proper study of the T-cell adaptive immune response were at hand and well known already several years ago an essential 'ingredient' in the cooking pot of CD was missing ( Figure 1). For many years it had been reported the presence of an autoantibody response in CD which was defined as antireticulin and then antiendomysium (EMA) [23][24][25] to characterize an 'ill'-defined reactivity to extracellular, matrix component of the small intestine.…”

Section: The Pathogenic Cascadementioning

confidence: 99%

“…We have indicated that other pathways, besides the activation of pathogenic T cells, are involved in the pathogenesis of CD. 21,22 In particular, there is a possible involvement of the IEL population. 38,39,42 These IELs are increased in number and appear to be involved in the epithelial destructive phase of CD.…”

Section: Targeting a Gt Therapy In CDmentioning

confidence: 99%