HLA-DQ2-restricted gluten-reactive T cells produce IL-21 but not IL-17 or IL-22.
We have analyzed the production of the effector cytokines interleukin (IL)-17, IL-21, and IL-22 in gluten-reactive CD4(+) T cells of celiac disease patients, either cultured from small intestinal biopsies or isolated from peripheral blood after an oral gluten challenge. Combining intracellular cytokine staining with DQ2-α-II gliadin peptide tetramer staining of intestinal polyclonal T-cell lines, we found that gluten-specific T cells produced interferon-γ (IFN-γ) and IL-21, but not IL-17 or IL-22, even if other T cells of the same lines produced these cytokines. Similarly, in DQ2-α-II-specific T cells in peripheral blood of gluten-challenged patients, very few stained for intracellular IL-17, whereas many cells stained for IFN-γ. We conclude that gluten-reactive T cells produce IL-21 and IFN-γ, but not IL-17. Their production of IL-21 suggests a role for this cytokine in the pathogenesis of celiac disease.
Bodd
M
M
Centre for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital-Rikshospitalet, Oslo, Norway. Michael.Bodd@rr-research.no
Ráki
M
M
Tollefsen
S
S
Fallang
L E
LE
Bergseng
E
E
Lundin
K E A
KE
Sollid
L M
LM
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002446:Celiac Disease / Q000276:immunology*; D002460:Cell Line; D005903:Gliadin / Q000276:immunology / Q000378:metabolism*; D005983:Glutens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism*; D007422:Intestines / Q000276:immunology / Q000473:pathology; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D000097043:Interleukin-22; D000098546:Interleukin-21
D005903:Gliadin; D005983:Glutens; D006683:HLA-DQ Antigens; D020381:Interleukin-17; D007378:Interleukins; D010446:Peptide Fragments; D000097043:Interleukin-22; D000098546:Interleukin-21; C053186:HLA-DQ2 antigen