EVIDENCE THAT INTESTINAL INTRAEPITHELIAL LYMPHOCYTES ARE ACTIVATED CYTOTOXIC T-CELLS IN CELIAC-DISEASE BUT NOT IN GIARDIASIS

To further define intraepithelial lymphocytes (IELs) in celiac disease CCD) and giardiasis, IELs were probed for the presence of cytolytic g ranules containing granzyme B (GrB) and T-cell-restricted intracellula r antigen (TIA)-1. The expression of TIA-I, GrB, CD3 (T-cell-receptor- associated complex, and Leu-7 (subset of natural killer cells) was stu died by a sensitive three-step immunoperoxidase technique. Stained IEL s were determined quantitatively, and results were expressed as number of stained IELs per 100 epithelial cells (ECs). The relative content in labeled lamina propria lymphocytes was determined and expressed as the percentage of all lamina propria cells counted. When compared with controls, CD3(+) and GrB(+) IELs were significantly increased (P < 0. 0004) in CD paralleled by an increase in TIA-II IELs (P < 0.0004), In CD, the highest numbers of IELs containing GrB were found in subjects with a flat mucosa (median, 38 IELs/100 ECs, P < 0.0004), followed by cases with shortened and blunted villi (median, 8 IELs/100 ECs, P < 0. 0004) and, finally, CD patients with an intact villous architecture (m edian, 0.5 IELs/100 ECs, P < 0.02), Except for cases with giardiasis, Leu-7(+) IELs were virtually absent in all groups as were GrB(+) IELs in the controls and in subjects with giardiasis, In the lamina propria of CD subjects, GrB(+) lymphocytes were also significantly increased (P < 0.001), whereas controls and cases with giardiasis were essential ly free of GI Bt cytotoxic T lymphocytes, The percentage of CD3(+) lam ina propria lymphocytes was nearly, equal irt all groups. in humans an d mice, extensive studies revealed a GrB expression to be absolutely r estricted to activated cytotoxic T lymphocytes and natural killer cell s, TLA-I, oil the other hand is considered a marker of resting T lymph ocytes possessing cytolytic potential, We therefore conclude that IELs are cytotoxic T cells that are in a resting state in the normal small bowel and irt giardiasis. In CD, they become activated as suggested b y the G-B positivity Of their granules.