T cells in peripheral blood after gluten challenge in coeliac disease

Abstract

Background: Current understanding of T cell epitopes in coeliac disease (CD) largely derives from intestinal T cell clones in vitro. T cell clones allow identification of gluten peptides that stimulate T cells but do not quantify their contribution to the overall gluten specific T cell response in individuals with CD when exposed to gluten in vivo. Aims: To determine the contribution of a putative dominant T cell epitope to the overall gliadin T cell response in HLA-DQ2 CD in vivo. Patients: HLA-DQ2+ individuals with CD and healthy controls. Methods: Subjects consumed 20 g of gluten daily for three days. Interferon c (IFN-c) ELISPOT was performed using peripheral blood mononuclear cells (PBMC) to enumerate and characterise peptide and gliadin specific T cells before and after gluten challenge. Results: In 50/59 CD subjects, irrespective of homo-or heterozygosity for HLA-DQ2, IFN-c ELISPOT responses for an optimal concentration of A-gliadin 57-73 Q-E65 were between 10 and 1500 per million PBMC, equivalent to a median 51% of the response for a ''near optimal'' concentration of deamidated gliadin. Whole deamidated gliadin and gliadin epitope specific T cells induced in peripheral blood expressed an intestinal homing integrin (a4b7) and were HLA-DQ2 restricted. Peripheral blood T cells specific for A-gliadin 57-73 Q-E65 are rare in untreated CD but can be predictably induced two weeks after gluten exclusion. Conclusion: In vivo gluten challenge is a simple safe method that allows relevant T cells to be analysed and quantified in peripheral blood by ELISPOT, and should permit comprehensive high throughput mapping of gluten T cell epitopes in large numbers of individuals with CD.

CD4 T Cell-Dependent Autoimmunity against a Melanocyte Neoantigen Induces Spontaneous Vitiligo and Depends upon Fas-Fas Ligand Interactions

“…For example, in celiac disease, large numbers of autoreactive gliadin-specific T cells are present in peripheral blood but only when disease is quiescent and the immunogenic Ag gluten is absent (65). Our findings address this issue directly by showing that patchiness persists even when the frequency of immunocompetent CD4 ϩ T cells is still relatively high, suggesting that the slow progression of lesions is likely to be limited by other factors.…”

Decreased numbers of circulating plasmablasts and differences in IgA1-plasmablast homing to skin in coeliac disease and dermatitis herpetiformis

“…Investigation of these HR is expected to reflect the final effector site of these cells [29][30][31][32]. Gluten-specific T cells in CD and DH have been shown to express b7-integrin interpreted as an indicator of gut-homing profile [46][47][48]. To our knowledge, the present study is the first to investigate HR expression on B cells in gluten enteropathy.…”

Celiac disease: pathogenesis of a model immunogenetic disease

“…In this regard, enteric viruses can alter intestinal permeability to "gluten" peptides and upregulate the production of type I and type II IFNs, leading to upregulation of HLA-DQ2 and HLA-DQ8 on DCs. This can be accompanied by tissue damage with increased release of tissue TGase and perhaps also an increased influx of "gluten"-specific T cells from the periphery (72). In this hypothetical scenario, enteric viruses (and perhaps other enteric pathogens) create an optimal milieu for the activation of the HLA-DQ2- and HLA-DQ8-restricted "gluten"-specific Th1 cell response when those peptides "innocently" enter the cellular and cytokine milieu of the mucosal microenvironment.…”