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J Immunol. 2016 Mar 15;196(6):2819-26. doi: 10.4049/jimmunol.1501152. Epub 2016 Feb 19.

Healthy HLA-DQ2.5+ Subjects Lack Regulatory and Memory T Cells Specific for Immunodominant Gluten Epitopes of Celiac Disease.

Author information

1
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway; and asbjorn.christophersen@rr-research.no.
2
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway; and.
3
Centre for Immune Regulation and Department of Immunology, University of Oslo and Oslo University Hospital, 0372 Oslo, Norway; and Department of Gastroenterology, Oslo University Hospital-Rikshospitalet, 0372 Oslo, Norway.

Abstract

Celiac disease (CD) is an HLA-associated disorder characterized by a harmful T cell response to dietary gluten. It is not understood why most individuals who carry CD-associated HLA molecules, such as HLA-DQ2.5, do not develop CD despite continuous gluten exposure. In this study, we have used tetramers of HLA-DQ2.5 bound with immunodominant gluten epitopes to explore whether HLA-DQ2.5(+) healthy individuals mount a specific CD4(+) T cell response to gluten. We found that gluten tetramer-binding memory cells were rare in blood of healthy individuals. These cells showed lower tetramer-binding intensity and no signs of biased TCR usage compared with gluten tetramer-binding memory T cells from patients. After sorting and in vitro expansion, only 18% of the tetramer-binding memory cells from healthy subjects versus 79% in CD patients were gluten-reactive upon tetramer restaining. Further, T cell clones of tetramer-sorted memory cells of healthy individuals showed lower gluten-specific proliferative responses compared with those of CD patients, indicating that tetramer-binding memory cells in healthy control subjects may be cross-reactive T cells. In duodenal biopsy specimens of healthy control subjects, CD4(+) T cells were determined not to be gluten reactive. Finally, gluten tetramer-binding cells of healthy individuals did not coexpress regulatory T cell markers (Foxp3(+) CD25(+)) and cultured T cell clones did not express a cytokine profile that indicated immune-dampening properties. The results demonstrate that healthy HLA-DQ2.5(+) individuals do not mount a T cell response to immunodominant gluten epitopes of CD.

PMID:
26895834
DOI:
10.4049/jimmunol.1501152
[Indexed for MEDLINE]
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