title: Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease.
abstract: OBJECTIVE
  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.
authors.affiliation: INSERM E9925, Faculté Necker, Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Jabri
authors.forename: N P
authors.initials: NP
authors.lastname: de Serre
authors.forename: C
authors.initials: C
authors.lastname: Cellier
authors.forename: K
authors.initials: K
authors.lastname: Evans
authors.forename: C
authors.initials: C
authors.lastname: Gache
authors.forename: C
authors.initials: C
authors.lastname: Carvalho
authors.forename: J F
authors.initials: JF
authors.lastname: Mougenot
authors.forename: M
authors.initials: M
authors.lastname: Allez
authors.forename: R
authors.initials: R
authors.lastname: Jian
authors.forename: P
authors.initials: P
authors.lastname: Desreumaux
authors.forename: J F
authors.initials: JF
authors.lastname: Colombel
authors.forename: C
authors.initials: C
authors.lastname: Matuchansky
authors.forename: H
authors.initials: H
authors.lastname: Cugnenc
authors.forename: M
authors.initials: M
authors.lastname: Lopez-Botet
authors.forename: E
authors.initials: E
authors.lastname: Vivier
authors.forename: A
authors.initials: A
authors.lastname: Moretta
authors.forename: A I
authors.initials: AI
authors.lastname: Roberts
authors.forename: E C
authors.initials: EC
authors.lastname: Ebert
authors.forename: D
authors.initials: D
authors.lastname: Guy-Grand
authors.forename: N
authors.initials: N
authors.lastname: Brousse
authors.forename: J
authors.initials: J
authors.lastname: Schmitz
authors.forename: N
authors.initials: N
authors.lastname: Cerf-Bensussan
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism*; D002446:Celiac Disease / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005434:Flow Cytometry; D006680:HLA Antigens / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007223:Infant; D019409:Interleukin-15 / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D037181:Lectins, C-Type; D008214:Lymphocytes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D019409:Interleukin-15; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011948:Receptors, Antigen, T-Cell; D000097625:HLA-E Antigens; C497869:KLRD1 protein, human