Intraepithelial and lamina propria lymphocytes show distinct patterns of apoptosis whereas both populations are active in Fas based cytotoxicity in coeliac disease

Background-Lamina propria (LPLs) and intraepithelial (IELs) lymphocytes are markedly increased in coeliac mucosa, and are thought to play a crucial ro le in the generation of villous atrophy in coeliac disease (CD). However, t he mechanisms by which they mediate the killing of enterocytes in this cond ition are still poorly characterised. Aim-We investigated Fas mediated cytotoxicity and apoptosis of both LPLs an d IELs, isolated from 10 untreated coeliac patients, 10 coeliac patients on a gluten free diet, and 10 biopsied controls. Methods-Fas and Fas ligand expression were assessed by flow cytometry and i mmunocytochemistry. Lymphocyte cytotoxicity against Fas expressing Jurkat c ells was determined by the jam test. The effect of the antagonist ZB4 anti- Fas antibody on apoptotic activity exerted by coeliac lymphocytes against e nterocytes was analysed. Lymphocyte apoptosis was assessed by oligonucleoso me ELISA. Results-LPLs and IELs showed increased apoptotic activity and higher levels of Fas ligand expression in untreated CD compared with treated CD patients and controls. Enterocyte apoptosis observed after coculturing coeliac lymp hocytes and enterocytes in the presence of ZB4 antibody was reduced. In act ive CD, LPLs manifested increased apoptosis whereas IELs showed decreased a poptosis. Conclusions-Our results support the involvement of the Fas/Fas ligand syste m in CD associated enterocyte apoptosis. Increased LPL apoptosis is likely to down-regulate mucosal inflammation whereas decreased IEL apoptosis could be responsible for autoimmune and malignant complications of CD.