Selective expansion of intraepithelial lymphocytes expressing the HLA-E-specific natural killer receptor CD94 in celiac disease
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Published on: December 15, 2011
B Jabri1, N P de Serre, C Cellier
1INSERM E9925, Faculté Necker, Paris, France.
Insights
In active celiac disease, a specific increase in intraepithelial lymphocytes (IELs) expressing the natural killer (NK) receptor CD94 is observed. This expansion may be linked to T-cell receptor activation and interleukin 15 signaling in the gut.
Area of Science:
- Gastroenterology
- Immunology
- Cell Biology
Background:
- Celiac disease is a gluten-induced enteropathy with T-cell infiltration in the gut lamina propria.
- The mechanism driving intraepithelial T-cell infiltration in celiac disease remains unclear.
Purpose of the Study:
- To characterize the specific subsets of intraepithelial lymphocytes (IELs) that expand during active celiac disease.
- To elucidate the mechanisms underlying IEL expansion in celiac disease.
Main Methods:
- Flow cytometry and immunohistochemistry were used to analyze IELs from 51 celiac patients and 50 controls.
- Monoclonal antibodies against T-cell and natural killer (NK) receptors were employed.
- In vitro studies investigated stimuli for NK receptor expression.
Main Results:
- A significant increase in CD94-expressing IELs, predominantly alpha beta T cells, was observed in active celiac disease compared to controls.
- The expression of other NK receptors on IELs remained unchanged.
- CD94 expression was induced in vitro by T-cell receptor activation and/or interleukin 15.
Conclusions:
- The gut epithelium supports the development of T cells expressing NK receptors.
- Active celiac disease shows a specific increase in IELs expressing CD94, an HLA-E-specific NK receptor.
- This increase is potentially related to T-cell receptor activation and interleukin 15 secretion.
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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