Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients.
Tetramers of MHC-peptide complexes are used for detection and characterization of antigen-specific T cell responses, but they require knowledge about both antigenic peptide and the MHC restriction element. The successful application of these reagents in human diseases involving CD4+ T cells is limited. Celiac disease, an intestinal inflammation driven by mucosal CD4+ T cells recognizing wheat gluten peptides in the context of disease-associated HLA-DQ molecules, is an ideal model to test the potential clinical use of these reagents. We investigated whether gluten-specific T cells can be detected in the peripheral blood of celiac disease patients using DQ2 tetramers. Nine DQ2+ patients and six control individuals on a gluten-free diet were recruited to the study. Participants consumed 160 g of gluten-containing bread daily for 3 days. After bread-challenge, gluten-specific T cells were detectable in the peripheral blood of celiac patients but not controls both directly by tetramer staining and indirectly by enzyme-linked immunospot. These T cells expressed the beta(7) integrin indicative of gut-homing properties. Most of the cells had a memory phenotype, but many other phenotypic markers showed a heterogeneous pattern. Tetramer staining of gluten-specific T cells has the potential to be used for diagnosis of celiac disease.
Ráki
Melinda
M
Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. melinda.raki@medisin.uio.no
Fallang
Lars-Egil
LE
Brottveit
Margit
M
Bergseng
Elin
E
Quarsten
Hanne
H
Lundin
Knut E A
KE
Sollid
Ludvig M
LM
D000328:Adult; D000368:Aged; D001939:Bread; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood* / Q000628:therapy; D002454:Cell Differentiation; D041981:Gastrointestinal Tract / Q000276:immunology*; D005983:Glutens / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008875:Middle Aged; D010641:Phenotype; D020836:Protein Structure, Quaternary; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D005983:Glutens; D007371:Interferon-gamma