Increased TIA1-Expressing Intraepithelial Lymphocytes in Cow's Milk Protein Intolerance

Abstract

Although a high level of intraepithelial lymphocytes (IELs) has been demonstrated in intestinal biopsies from children with cow's milk protein intolerance (CMPI), the properties of IELs in food-sensitive enteropathies remain unclear. In the present study, we analyzed the cytotoxic potential of IELs in CMPI, using a monoclonal antibody directed against the cytotoxic granule-associated protein TIA1. The study included 18 duodenal biopsies from 10 children previously diagnosed with CMPI and on a cow's milk-free diet of various duration. Six normal duodenal biopsies from children free of food intolerance served as controls. Immunostaining of formalin-fixed tissues was used to determine in the intraepithelial compartment (1) the number of TIA1-expressing cells per 100 epithelial cells, (2) the number of IELs per 100 epithelial cells, (3) the ratio of TIA1-expressing IELs (TIA1/IEL ratio). In CMPI, the number of IELs and TIA1-positive cells, as well as the TIA1/IEL ratio was significantly increased compared with controls. Moreover, a negative correlation between the TIA1/IEL ratio and the duration of the diet was observed. These results suggest that the recruitment of IELs with cytotoxic potential is increased in CMPI, and that IEL-mediated cytotoxicity could be involved in the pathogenesis of the disease.