Changing jejunal γδ T cell receptor (TCR)-bearing intraepithelial lymphocyte density in coeliac disease

Abstract

The function of jejunal intraepithelial γδ+ T cells is obscure, but they are commonly implicated as playing a role in inflammatory and autoimmune conditions. In coeliac disease (COD), there are controversial reports as to gluten dependency of these cells. We have now studied the small bowel mucosal intraepithelial T cell densities, and the ratios of γδ+ to CD3+ T cells and γδ+ to αβ+ T cells during early disease development and on a gluten-free diet. Nine children initially excluded for CoD were followed up and rebiopsy after 0.8-4.5 years showed mucosal deterioration. Further, 21 biopsy specimens from newly diagnosed CoD patients were studied, together with 20 specimens taken from children on a gluten-free diet. During CoD development the density of γδ+ and αβ+ T cells as well as the ratios of γδ+ to CD3+ T cells and γδ+ to αβ+ T cells increased. In the latent stage of CoD when the small bowel mucosal architecture was still normal, two children had clearly normal densities of γδ+ (<2.5 cells/100 epithelial cells) and αβ+ (<25.0 cells/100 epithelial cells) T cells, and low ratios as well. In patients with newly diagnosed CoD the densities decreased significantly on a long-term gluten-free diet. We conclude that the density of intraepithelial γδ+ T cells as well as αβ+ T cells in CoD is gluten- dependent. CoD can develop in a child ingesting normal amounts of gluten and having normal jejunal mucosal morphology on biopsy and a normal density of γδ+ T cells.