Intraepithelial gamma delta T-cell-receptor lymphocytes and genetic susceptibility to coeliac disease.

Although the proportion of gamma delta T-cell-receptor (TCR)-bearing intraepithelial lymphocytes is increased in the jejunum of patients with active coeliac disease, an abnormality thought to be specific among those with gluten-sensitive enteropathy, the factors influencing gamma delta TCR expression remain uncertain. We examined the relation between genetic factors associated with coeliac disease and intraepithelial gamma delta T lymphocyte distribution in both coeliac patients and their healthy first-degree relatives. 41% (45/109) of healthy relatives had an increased density of gamma delta T cells in their mucosa and 66% had an increased density of alpha beta T cells. By contrast with alpha beta T cells, the density of gamma delta cells was significantly associated with genetic markers for coeliac disease susceptibility (DR3, DQA, and DQB). We also found a dose effect of DQA and DQB genes on the number of intraepithelial gamma delta T cells. An increased density of gamma delta T cells in normal jejunal mucosa of a healthy individual with appropriate genetic determinants might be necessary for the development of the typical lesions of coeliac disease. Routine jejunal histological studies should include gamma delta T-cell counts, thus allowing early detection of coeliac disease latency.