This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Oberhuber, G. Articles by Radaszkiewicz, T. Search for Related Content PubMed PubMed Citation Articles by Oberhuber, G. Articles by Radaszkiewicz, T.

American Journal of Pathology, Vol 148, 1351-1357, Copyright © 1996 by American Society for Investigative Pathology

REGULAR ARTICLES

Evidence that intestinal intraepithelial lymphocytes are activated cytotoxic T cells in celiac disease but not in giardiasis

G Oberhuber, H Vogelsang, M Stolte, S Muthenthaler, AJ Kummer and T Radaszkiewicz
Department of Clinical Pathology, University of Vienna Medical School, Austria.

To further define intraepithelial lymphocytes (IELs) in celiac disease (CD) and giardiasis, IELs were probed for the presence of cytolytic granules containing granzyme B (GrB) and T-cell-restricted intracellular antigen (TIA)-1. The expression of TIA-1, GrB, CD3 (T- cell-receptor-associated complex), and Leu-7 (subset of natural killer cells) was studied by a sensitive three-step immunoperoxidase technique. Stained IELs 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-1+ 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 (median, 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 essentially free of GrB+ cytotoxic T lymphocytes. The percentage of CD3+ lamina propria lymphocytes was nearly equal in all groups. In humans and mice, extensive studies revealed a GrB expression to be absolutely restricted to activated cytotoxic T lymphocytes and natural killer cells. TIA-1, on the other hand, is considered a marker of resting T lymphocytes possessing cytolytic potential. We therefore conclude that IELs are cytotoxic T cells that are in a resting state in the normal small bowel and in giardiasis. In CD, they become activated as suggested by the GrB positivity of their granules.

This article has been cited by other articles:

				A. Alaedini and P. H.R. Green Narrative Review: Celiac Disease: Understanding a Complex Autoimmune Disorder Ann Intern Med, February 15, 2005; 142(4): 289 - 298. [Abstract] [Full Text] [PDF]

				K. G.-E. Scott, L. C. H. Yu, and A. G. Buret Role of CD8+ and CD4+ T Lymphocytes in Jejunal Mucosal Injury during Murine Giardiasis Infect. Immun., June 1, 2004; 72(6): 3536 - 3542. [Abstract] [Full Text] [PDF]

				C. Gianfrani, R. Troncone, P. Mugione, E. Cosentini, M. De Pascale, C. Faruolo, S. Senger, G. Terrazzano, S. Southwood, S. Auricchio, et al. Celiac Disease Association with CD8+ T Cell Responses: Identification of a Novel Gliadin-Derived HLA-A2-Restricted Epitope J. Immunol., March 1, 2003; 170(5): 2719 - 2726. [Abstract] [Full Text] [PDF]

				K. G.-E. Scott, M. R. Logan, G. M. Klammer, D. A. Teoh, and A. G. Buret Jejunal Brush Border Microvillous Alterations in Giardia muris-Infected Mice: Role of T Lymphocytes and Interleukin-6 Infect. Immun., June 1, 2000; 68(6): 3412 - 3418. [Abstract] [Full Text] [PDF]

				E C Ebert Giardia induces proliferation and interferon gamma  production by intestinal lymphocytes Gut, March 1, 1999; 44(3): 342 - 346. [Abstract] [Full Text] [PDF]

				A. Chott, W. Haedicke, I. Mosberger, M. Fodinger, K. Winkler, C. Mannhalter, and H.-K. Muller-Hermelink Most CD56+ Intestinal Lymphomas Are CD8+CD5- T-Cell Lymphomas of Monomorphic Small to Medium Size Histology Am. J. Pathol., November 1, 1998; 153(5): 1483 - 1490. [Abstract] [Full Text] [PDF]

				A. Anumanthan, A. Bensussan, L. Boumsell, A. D. Christ, R. S. Blumberg, S. D. Voss, A. T. Patel, M. J. Robertson, L. M. Nadler, and G. J. Freeman Cloning of BY55, a Novel Ig Superfamily Member Expressed on NK Cells, CTL, and Intestinal Intraepithelial Lymphocytes J. Immunol., September 15, 1998; 161(6): 2780 - 2790. [Abstract] [Full Text] [PDF]

				B. Arnulf, C. Copie-Bergman, M.-H. Delfau-Larue, A. Lavergne-Slove, J. Bosq, J. Wechsler, M. Wassef, C. Matuchansky, B. Epardeau, M. Stern, et al. Nonhepatosplenic gamma delta T-Cell Lymphoma: A Subset of Cytotoxic Lymphomas With Mucosal or Skin Localization Blood, March 1, 1998; 91(5): 1723 - 1731. [Abstract] [Full Text] [PDF]