Gluten activation of peripheral blood T cells induces a Th0-like cytokine pattern in both coeliac patients and controls

Abstract

SUMMARYCoeliac disease is apparently a T cell-mediated disease, precipitated in the proximal small intestine of susceptible individuals by gluten. Preferential presentation of gluten peptides most probably takes place in coeliac mucosa by the disease-associated HLA-DQ2 and -DQ8 molecules. In peripheral blood, however, both HLA-DR, -DQ and -DP-restricted T cell responses to gluten have been observed. We examined gluten-specific T cell clones (TCC) derived from peripheral blood for cytokine production to see if their profiles were related to the HLA restriction or the disease state of the donors. As previously found for mucosal TCC, the main product was interferon-gamma (IFN-), often with additional IL-4, IL-5, IL-6, IL-10, tumour necrosis factor, and transforming growth factor-beta. Regardless of restriction element or disease state, gluten-reactive TCC from peripheral blood therefore seem to secrete cytokines compatible with a Th0 profile.

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

“…Our findings, showing that MNC from CD patients are able to produce IFNÁ, TNF· and IL-4 when stimulated with gluten, strengthen the idea that the gluteninduced cytokine production is important in the pathogenesis of the disease [3,12]. In addition, in this paper it is shown that IL-4 is produced by gluten-stimulated MNC from both CD patients and their DQ2-positive relatives.…”

“…As reported by different groups a number of cytokines could play a central role in the experimental and spontaneous immunologically mediated enteropathies [3,[9][10][11]. In particular, gluten-reactive, HLA-restricted T cell clones obtained from peripheral blood lymphocytes of healthy donors and CD patients seem to be able to secrete cytokines compatible with a Th0 profile [12]. Data reported herein seem to suggest that interleukin-4 (IL-4), which, as recently reported [13], is involved in the pathogenesis of the immunemediated lesions of mucosal epithelial tissues could play a role in the pathogenesis of CD.…”

“…T cell clones from peripheral blood of DQ2-positive celiac patients and controls seem to be able to secrete cytokines compatible with a Th0 profile [12] as defined by Romagnani [22]. The above-reported findings demonstrating that in vitro gluten stimulation is able to induce the activation of TÁ‰ lymphocytes prompt us to investigate the pattern of cytokines produced by gluten-stimulated MNC from DQ2-positive and negative subjects.…”

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.…”

IL-4-regulated enteropathy in an intestinal nematode infection

“…TNF has been shown to be critical in many Th1-mediated models of intestinal pathology [15,16,18,19,30], whereas the novel feature in T. spiralis infections is that TNF appears to play a role in IL-4-regulated pathology. There is evidence of a role for Th2 cytokines in enteropathies of other etiologies; elevated levels of IL-4, IL-5, IL-6 and IL-10 and decreased levels of IFN-+ and IL-2 have been demonstrated in a number of intestinal pathologies [17,31].…”