Are Intraepithelial Lymphocytes in Celiac Mucosa Responsible for Inducing Programmed Cell Death (Apoptosis) in Enterocytes? Histochemical Demonstration of Perforins in Cytoplasmic Granules of Intraepithelial Lymphocytes

Abstract

ABSTRACTBackground:Programmed cell death refers to the genetically determined processes by which cells die in response to physiologic extracellular and intracellular signals, morphologically described as apoptosis. In physiologic and pathologic circumstances this process may involve effector and target cells.Methods:To identify serine esterase granules in intraepithelial lymphocytes, fresh‐frozen human small intestine mucosal sections from normal and celiac‐affected mucosa were incubated with substrate‐specific N‐α‐benzyloxy‐carbonyl‐L‐lysine thiobenzyl (BLT) and a chromogen (4 Benzoylamino‐2,5‐diethoxybenzene‐dazonium chloride hemi [zinc chloride] salt as capture agent and were examined by light microscopy.Results:Normal mucosa showed an occasional intraepithelial lymphocyte with BLT‐positive intracytoplasmic granules. Some large mononuclear cells of the lamina propria were similarly stained. Many more intraepithelial lymphocytes were BLT‐positive among the surface enterocytes of untreated celiac mucosa. Lamina propria mononuclear cells close to the basal layer of crypt cells also appeared to be increased.Conclusions:The histochemical identification of BLT‐positive esters within intraepithelial lymphocytes suggests their involvement in enterocyte death under physiologic conditions. The increased BLT‐positive intraepithelial lymphocytes found in the celiac mucosa may be related to the known increase in cytotoxic intraepithelial lymphocytes in untreated celiac disease.