T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC)

Abstract

The immune response of PBMC to gliadin was investigated in patients with coeliac disease (CoD) by examining proliferation, MHC restriction and cytokine production. Gliadin induced low levels of proliferation in 63% of eight untreated patients, 32% of 28 treated patients and 35% of 31 healthy control subjects. In MHC restriction studies, the proliferative response to gliadin was inhibited (range 47-98% inhibition) in the presence of a MoAb to HLA-DR in each of three coeliac and three control donors studied. Using flow cytometry, increased expression of activation markers (HLA-DR and IL-2R) was demonstrated on gliadin-stimulated T cells from four of nine coeliac patients and three of seven healthy control donors. Cytokines were studied in culture supernatants using ELISA. Gliadin was a potent inducer of IL-6 and IL-10 in 100% of coeliac patients and controls, whereas IL-4 was not produced in either subject group. Gliadin induced IL-2 production in 40% of untreated patients, 42% of treated patients and 35% of healthy control donors. Interferon-gamma (IFN-gamma) in gliadin-stimulated cultures was found only in coeliac patients, observed in 33% of untreated patients and 25% of treated patients. Spontaneous secretion of both IL-2 and IFN-gamma was found more frequently in patients with untreated disease (87% of cases versus 21% of controls for IFN-gamma and 40% versus 0% for IL-2). These results suggest, as manifest by IFN-gamma production, that gliadin stimulates a Th1/Th0-like response in coeliac patients and a Th0-like response in healthy controls.

Highly Efficient Gluten Degradation by Lactobacilli and Fungal Proteases during Food Processing: New Perspectives for Celiac Disease

“…IFN-␥ production is a Th1-specific event (2), whereas proliferation is an index of T-cell activation. Indeed, the proliferation of PBMCs of CD patients is inhibited by anti-DR antibody, indicating that class II molecules are involved in the presentation of gliadin peptides to peripheral T cells (28). IFN-␥ coordinates many aspects of the innate and adaptive immune responses, and it is the principal cytokine produced by ␣␤ CD4 ϩ reactive T cells upon gluten activation (26,27,32,45).…”

Immune Phenotype of Children with Newly Diagnosed and Gluten-Free Diet-Treated Celiac Disease

“…Indeed, total T lymphocyte prevalence was lower at the periphery [7] while increased in biopsy samples [3,8,9] in CD compared to age-matched controls. This finding was accompanied by an increased prevalence of activated lymphocytes in CD irrespective of whether it was measured in peripheral blood [7,[10][11][12][13] or biopsy specimens [14,15]. Simultaneously with these alterations marked abnormalities of function and prevalence of regulatory T cells (Tregs), the major suppressor cells of adaptive immune system were observed in blood and biopsy specimens of patients with CD, respectively [16][17][18].…”

Molecular Dissection of the Tissue Transglutaminase Autoantibody Response in Celiac Disease

“…C eliac disease (CD) 4 is characterized by intestinal mucosal injury and malabsorption precipitated by dietary exposure to wheat gluten and similar proteins in rye and barley (1), with gliadins, specific antigenic determinants found in wheat gluten (2), playing a prominent role. Patients suffering from CD have serum Abs recognizing gliadin as well as an endomysial autoantigen, recently identified as being tissue transglutaminase (tTG) (3), an enzyme catalyzing Ca 2ϩ -dependent cross-linking between glutamine residues in peptides and some polyamines and primary amino groups.…”

“…The Ab levels against both Ags increase on exposure to glutens and decrease on a gluten-free diet. Gliadin peptides have been shown to be presented to Ag-specific T cells at the intestinal level by HLA class II Ags (4), and this may explain the strong association with HLADQ2 (5). The role of tTG in the disease is still unknown, although it has been proposed that this enzyme is involved in the activation of gliadin peptides (6), thus leading to their toxicity.…”