Gastroenterology

Gastroenterology

Volume 118, Issue 5, May 2000, Pages 867-879
Gastroenterology

Alimentary Tract
Selective expansion of intraepithelial lymphocytes expressing the HLA-E–specific natural killer receptor CD94 in celiac disease,☆☆

https://doi.org/10.1016/S0016-5085(00)70173-9Get rights and content

Abstract

Background & Aims: Celiac disease is a gluten-induced enteropathy characterized by the presence of gliadin-specific CD4+ T cells in the lamina propria and by a prominent intraepithelial T-cell infiltration of unknown mechanism. The aim of this study was to characterize the subset(s) of intraepithelial lymphocytes (IELs) expanding during active celiac disease to provide insights into the mechanisms involved in their expansion. Methods: Flow-cytometric analysis of isolated IELs and/or immunohistochemical staining of frozen sections were performed in 51 celiac patients and 50 controls with a panel of monoclonal antibodies against T-cell and natural killer (NK) receptors. In addition, in vitro studies were performed to identify candidate stimuli for NK receptor expression. Results: In normal intestine, different proportions of IELs, which were mainly T cells, expressed the NK receptors CD94/NKG2, NKR-P1A, KIR2D/3D, NKp46, Pen5, or CD56. During the active phase of celiac disease, the frequency of CD94+ IELs, which were mostly αβ T cells, was conspicuously increased over controls. In contrast, the expression of other NK markers was not modified. Furthermore, expression of CD94 could be selectively induced in vitro by T-cell receptor activation and/or interleukin 15, a cytokine produced by intestinal epithelial cells. Conclusions: The gut epithelium favors the development of T cells that express NK receptors. In active celiac disease, there is a specific and selective increase of IELs expressing CD94, the HLA-E–specific NK receptor that may be related to T-cell receptor activation and/or interleukin 15 secretion.

GASTROENTEROLOGY 2000;118:867-879

Abbreviations

EC
epithelial cell
FACS
fluorescence-activated cell sorter
FITC
fluorescein isothiocyanate
GFD
gluten-free diet
IEL
intraepithelial lymphocyte
IFN-γ
interferon gamma
MHC
major histocompatibility complex
NK
natural killer
PBL
peripheral blood lymphocyte
PE
phycoerythrin
TCR
T-cell receptor
T-IEL
IEL expressing T-cell receptor
TNF
tumor necrosis factor

Cited by (0)

Address requests for reprints to: Bana Jabri, M.D., Department of Molecular Biology, Schultz Laboratory, Princeton University, Washington Road, Princeton, New Jersey 08544. e-mail: [email protected]; or Nadine Cerf-Bensussan, M.D., INSERM E9925, Faculté Necker, 156, rue de Vangirard, 75730 Paris Cedex 15, France. e-mail: [email protected].

☆☆

Supported by grants from L'Association pour la Recherche contre le Cancer (contrats ARC 9216, 9962), Assistance Publique Hôpitaux de Paris (PHRC AOM96082), and la Société Nationale Française de Gastroentérologie.

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