Gluten Stimulation Induces an in vitro Expansion of Peripheral Blood Tγδ Cells from HLA-DQ2-Positive Subjects of Families of Patients with Celiac Disease

Abstract

The intestinal gluten sensitivity formally known as celiac disease (CD) is characterized by an evident involvement of local immune response and it is associated with the expression of HLA-DQ2 allele. The major role in the disease seems to be played by the T lymphocyte population bearing γδ T cell receptor (Tγδ cells) which are increased both in peripheral blood and intestinal mucosae of celiac patients. In this paper data on the effects of in vitro gluten stimulation on lymphocytes expressing the Tγδ phenotype are reported. Gluten seems to be able to induce the expansion of the Tγδ cell population both in CD patients and their HLA-DQ2-positive asymptomatic relatives, in spite of the absence of clinical evidence of the disease. In addition, the evaluation of gluten-induced cytokine production shows that interleukin-4 could be implied in the early phases of pathogenesis of CD.

Serum cytokine elevations in celiac disease: Association with disease presentation

“…Many in vitro studies have demonstrated that gluten (gliadin) induces sustained T h type 1 pro-inflammatory cytokine production [6,16,24,[31][32][33]. The T h type 1 response to dietary gluten in the small intestinal mucosa most likely drives the lymphocytic and monocytic infiltration of the lamina propria.…”

Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency

“…The Type 1 response in the small intestinal mucosa to dietary gluten drives the typical lymphocyte and monocyte infiltration (20). Moreover, many studies have demonstrated that gluten induces a sustained Type 1 pro‐inflammatory cytokine production in vitro , as Tcells may be able to release variable amounts of T helper Type 2 (Th2) cytokines (15–20).…”

“…However, high TNF‐α and IFN‐γ production by mucosal and peripheral blood cells is found in both CD and IgAD (15–17). In fact, cells producing a number of individual cytokines, in particular Type 1, pro‐inflammatory cytokines such as IFN‐γ have been found in the immunologically mediated lesions of celiac disease by different groups (15–18). In addition, studies of lamina propria T cells have indicated that gluten reactive T cells have a cytokine profile dominated by IFN‐γ and TNF‐α (15, 17).…”

HLA and disease

“…Heterodimer DQA1*0501-DQB1*0201/02 Dutch [65] DQ2 Homozygotes, DQA1*05-DQB1*02/DQA1*0201-DQB1*02 heterozygotes France [66] HLA-DQ2 (DQA1*0501/DQB1*0201) and DR53 Italy [67] HLA-DQ2 Netherlands [68] HLA-DQ2.5/2.5 homozygotes, HLA-DQ2.5/2.2 heterozygotes Norway [69] HLA-DQ2 (DQA 1*0501, DQB 1*0201) Spain [70] HLA-DRB1*04 (DR4) *These are some of the representative population studies from various continents.…”