INTRAEPITHELIAL LYMPHOCYTES IN NORMAL HUMAN INTESTINE DO NOT EXPRESS PROTEINS ASSOCIATED WITH CYTOLYTIC FUNCTION

Human small intestine contains a very large population of intraepithel ial T lymphocytes (IELs) that are oligoclonal, appear functionally to be cytolytic T cells, and may contribute to the normal. and pathologic al turnover of intestinal epithelial cells, This report addresses the cytolytic function of IELs in normal small intestine by examining thei r expression of molecules that carry out cell-mediated cytolysis, Immu nohistochemical analyses of granzyme B, perforin, Fas ligand, and tumo r necrosis factor-a demonstrated these proteins were not expressed by small intestinal IELs in situ, These proteins also were not expressed by colonic IELs or by lamina propria lymphocytes in the small or large intestine, Granzyme A, however, was expressed by a large fraction of IELs. In contrast to these in situ results, isolated and in vitro acti vated IELs were shown to express effector proteins consistent with cyt olytic T cells, including granzyme B, Fas ligand, tumor necrosis facto r-alpha, and interferon-gamma, These results are most consistent with the vast majority of IELs in normal human small intestine being restin g cytolytic T cells and suggest that these cells do not contribute to the apoptotic cell death of epithelial cells in normal intestine.