T Cells in Celiac Disease

Abstract

Celiac disease is a human T cell mediated autoimmune-like disorder caused by exposure to dietary gluten in genetically predisposed individuals. This review will discuss how a CD4 T cell responses directed against an exogenous antigen can cause an autoreactive B-cell response and participate in the licensing of intraepithelial lymphocytes to kill intestinal epithelial cells. Furthermore, the review will examine the mechanisms by which intraepithelial cytotoxic T cells mediate tissue destruction in celiac disease.

Diverse developmental pathways of intestinal intraepithelial lymphocytes

“…However, these cells are restricted to the lamina propria and do not seem to directly cause disease pathology 109 . By contrast, conventional CD8αβ + TCRαβ + IEL populations are markedly expanded and activated but do not seem to be gluten specific 108 . In healthy individuals, conventional CD8αβ + TCRαβ + IELs express inhibitory NK cell receptors including CD94–NKG2A 110,111 , whereas in patients with coeliac disease, increased levels of IL-15 upregulate the expression of activating NK cell receptors including NKG2C and NKG2D.…”

“…Coeliac disease is an inflammatory disorder in which a subset of genetically susceptible individuals who express HLA-DQ2 or HLA-DQ8 develop T H 1 cell-type inflammation in the small intestine, leading to villous atrophy and subsequent nutrient malabsorption 108 . Massive expansion of intestinal IEL populations is a hallmark of the disease.…”

Elevated serum interleukin‐2 after gluten correlates with symptoms and is a potential diagnostic biomarker for coeliac disease

“…The use of acute single‐dose oral food challenge is well established as an informative diagnostic manoeuvre and trial monitoring approach for food allergy, but has not previously been shown to be useful in coeliac disease . Coeliac disease is caused by ingestion of dietary gluten and activation of gluten‐specific CD4 + T cells; chronic gluten exposure results in characteristic histological abnormalities in the duodenal mucosa and production of autoantibodies specific for transglutaminase . Symptoms caused by gluten in coeliac disease are generally considered nonspecific, and delayed for days or weeks after gluten is reintroduced into the diet .…”

“…1,2 Coeliac disease is caused by ingestion of dietary gluten and activation of gluten-specific CD4 + T cells; chronic gluten exposure results in characteristic histological abnormalities in the duodenal mucosa and production of autoantibodies specific for transglutaminase. 3 Symptoms caused by gluten in coeliac disease are generally considered nonspecific, and delayed for days or weeks after gluten is reintroduced into the diet. 4,5 Thus, acute provocation testing has not played a role in the diagnosis of coeliac disease.…”

Clustering based approach for population level identification of condition-associated T-cell receptor β-chain CDR3 sequences

“…To evaluate the overall effectiveness of the method in identifying condition-associated CDR3s, we looked closely at the set of differentially enriched CDR3βs and compared them to known celiac disease associated CDR3β sequences in the literature. The detected lists of enriched CDR3βs had significantly increased usage of previously reported TRBV-genes in gluten-reactive CDR3β sequences (Qiao et al, 2011(Qiao et al, , 2013Broughton et al, 2012;Jabri and Sollid, 2017;Han et al, 2013) (Qiao et al, 2011(Qiao et al, , 2013 (Figure 5c and d, Figure 3Sc and d) , the method identified other previously unreported over used genes such as TRBV03-01 with previously unappreciated per-position amino acid usage patterns in the detected enriched CDR3s (Figure 5c), the detailed analysis of which may provide insights on their targets and overall significance in the pathogenesis of celiac disease. In addition, except in the nucleotide subsequence based analysis of CD Gut, the list of enriched CDR3βs from both CD PBMC and CD Gut contained significantly high number of previously reported CD-associated CDR3β sequences by Qiao et al, Han et al and Petersen et al (Qiao et al, 2011;Han et al, 2013;Petersen et al, 2014) than was expected by chance, as determined by both using a randomization test or a straight forward comparison to the proportion of previously known celiac disease associated CDR3s in the total repertoire of the combined dataset of all samples (see Tables 2 and 3, see supplementary Tables 1S and 2S for the list of previously known celiac disease associated CDR3 identified by the method).…”