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Cited by 261Celiac Disease Research and ManagementImmune Cell Function and InteractionInflammatory Bowel Disease

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

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Jabri, Bana, De Serre, Natacha Patey–Mariaud, Cellier, Christophe, Evans, Kelly, Gache, Cécile, Carvalho, Carla, Mougenot, Jean–François, Allez, Matthieu +14 more·2000·Gastroenterology
DOI 10.1016/s0016-5085(00)70173-9PMC PMC7095198
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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 alphabeta 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.

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  • In healthy individuals, CD8αβ+ TCRαβ+ IELs express the inhibitory NK receptors CD94/NKG2A, with a low expression of activating receptor NKG2D.

    “In healthy individuals, CD8αβ+ TCRαβ+ IELs express the inhibitory NK receptors CD94/NKG2A, with a low expression of activating receptor NKG2D [304, 305].”

    From Guidelines for the use of flow cytometry and cell sorting in immunological studies (third edition) (2021) · cites this paper as [304]

    The Results sections report CD94 on 27% of normal T-IELs, show that most CD94+ IELs in controls express TCRαβ, and find NKG2A on 29% ± 18% of CD94+ IELs in normal controls. They do not establish this expression specifically in CD8αβ+ cells or report low expression of NKG2D; a search for NKG2D found no measurement of it. (LLM, conf=0.87)

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  1. [16]Cerf-Bensussan N Jabri B Guy-Grand D Subsets of intraepithelial lymphocytes in normal intestine and in coeliac disease Mäki M Collin P Visakopi JK Proceedings of the seventh International Symposium on Coeliac Disease 1997 Vammalan Kirjapaino Oy Vammala, Finland 291 309

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Authors
Jabri, B., De Serre, N. P., Cellier, C., Evans, K., Gache, C., Carvalho, C., Mougenot, J., Allez, M., Jian, R., Desreumaux, P., Colombel, J., Matuchansky, C., Cugnenc, H., Lopez–Botet, M., Vivier, E., Moretta, A., Roberts, A. I., Ebert, E. C., Guy–Grand, D., Brousse, N., Schmitz, J., & Cerf–Bensussan, N.
Affiliations
Hôpital Necker-Enfants Malades (FR)
ORCID
Venue
Gastroenterology
Publisher
Elsevier BV
Published
2000-05
Volume
118
Issue
5
Pages
867-879
ISSN
0016-5085 (ISSN-L)
DOI
10.1016/s0016-5085(00)70173-9
PMC
PMC7095198
OpenAlex
W2098035977
Cited by
261
References
74
Citations by year
2026: 4 · 2025: 5 · 2024: 11 · 2023: 3 · 2022: 7 · 2021: 11 · 2020: 7 · 2019: 5 · 2018: 9 · 2017: 4 · 2016: 4 · 2015: 12 · 2014: 11 · 2013: 8 · 2012: 7
FWCI
12.44
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Gastroenterology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Gastroenterology › Celiac Disease Research and Management
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
Keywords
celiac disease, intraepithelial lymphocytes, CD94, HLA-E, natural killer receptors, NK cell receptors, IL-15, T cell receptor stimulation, alpha beta T cells, intestinal epithelium
MeSH terms
HLA-E Antigens, Adult, Celiac Disease, Cells, Cultured, Child, Child, Preschool, Flow Cytometry, HLA Antigens, Humans, Infant, Intestinal Mucosa, Killer Cells, Natural, Lymphocytes, Membrane Glycoproteins, Middle Aged, Receptors, Antigen, T-Cell, T-Lymphocytes, Histocompatibility Antigens Class I, Antigens, CD, Interleukin-15, Lectins, C-Type, NK Cell Lectin-Like Receptor Subfamily D

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