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

Background: 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 eff ector acid target cells. Methods: To identify serine esterase granules in intraepithelial lymphocytes, fresh-frozen human small intestine mu cosal sections from normal and celiac-affected mucosa were incubated w ith substrate-specific N-alpha-benzyloxy-carbonyl-L-lysine thiobenzyl (BLT) and a chromogen (4 Benzoylamino-2,5-diethoxybenzene-dazonium chl oride hemi [zinc chloride] salt as capture agent and were examined by light microscopy. Results: Normal mucosa showed an occasional intraepi thelial lymphocyte with BLT-positive intracytoplasmic granules. Some l arge mononuclear cells of the lamina propria were similarly stained. M any more intraepithelial lymphocytes were BLT-positive among the surfa ce enterocytes of untreated celiac mucosa. Lamina propria mononuclear cells close to the basal layer of crypt cells also appeared to be incr eased. Conclusions: The histochemical identification of BLT-positive e aters within intraepithelial lymphocytes suggests their involvement in enterocyte death under physiologic conditions. The increased BLT-posi tive intraepithelial lymphocytes found in the celiac mucosa may be rel ated to the known increase in cytotoxic intraepithelial lymphocytes in untreated celiac disease.