CD4+CD8+ human small intestinal T cells are decreased in coeliac patients, with CD8 expression downregulated on intra-epithelial T cells in the active disease.

Abstract

The intestinal lesion of coeliac disease is thought to be initiated and exacerbated by dysregulation of local T-lymphocyte sub-populations. This study examines changes in intestinal T cells from coeliac patients, with a particular focus on CD4CD8 T cells, immunoregulatory cells normally found in relatively high proportions in the small intestine. Cells were obtained from duodenal biopsies from active and treated coeliac patients using chelating and reducing agents (epithelial layer) followed by collagenase treatment (lamina propria). Cell yield and viability were assessed and flow cytometric analysis was used to examine CD4CD8 T cells and to quantify CD8 expression. Surprisingly, total T-cell yields in the epithelial layer did not increase in active coeliac disease although enterocyte counts decreased significantly, giving an appearance of infiltration. In active coeliac patients, CD4CD8 T cell percentages were significantly decreased in both the epithelial layer and lamina propria. Levels of CD8 expression by CD4CD8 T cells in the epithelial layer were decreased significantly in patients with active coeliac disease. CD4CD8 T cell proportions did not return to normal in treated coeliac patients whose villous architecture had responded to gluten withdrawal. No increase of intra-epithelial lymphocytes in the coeliac lesion may require us to reconsider the definition of coeliac disease as an inflammatory condition. Low CD4CD8 populations in treated as well as untreated coeliac patients indicate that these T cells are inherently absent in individuals genetically predisposed to coeliac disease.