In Vitro-Deranged Intestinal Immune Response to gliadin in type 1 diabetes

Dietary gluten has been associated with an increased
risk of type 1 diabetes. We have evaluated inflammation
and the mucosal immune response to gliadin in the
jejunum of patients with type 1 diabetes. Small intestinal
biopsies from 17 children with type 1 diabetes
without serological markers of celiac disease and from
50 age-matched control subjects were examined by immunohistochemistry.
In addition, biopsies from 12 type
1 diabetic patients and 8 control subjects were cultured
with gliadin or ovalbumin peptic-tryptic digest and examined
for epithelial infiltration and lamina propria
T-cell activation. The density of intraepithelial CD3(+)and gammadelta (+) cells and of lamina propria CD25(+) mononuclear
cells was higher in jejunal biopsies from type 1 diabetic
patients versus control subjects. In the patients' biopsies
cultured with peptic-tryptic gliadin, there was epithelial
infiltration by CD3(+) cells, a significant increase
in lamina propria CD25(+) and CD80(+) cells and enhanced
expression of lamina propria CD54 and crypt HLA-DR.
No such phenomena were observed in control subjects,
even those with celiac disease-associated HLA haplotypes.
In conclusion, signs of mucosal inflammation
were present in jejunal biopsies from type 1 diabetic
patients, and organ culture studies indicate a deranged
mucosal immune response to gliadin.