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.
Holm
K
K
Department of Clinical Sciences, University of Tampere, Finland.
Mäki
M
M
Savilahti
E
E
Lipsanen
V
V
Laippala
P
P
Koskimies
S
S
D000483:Alleles; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006684:HLA-DR Antigens / Q000032:analysis; D006239:Haplotypes; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000235:genetics*
D005819:Genetic Markers; D006684:HLA-DR Antigens; D016692:Receptors, Antigen, T-Cell, gamma-delta