title: Tetramer visualization of gut-homing gluten-specific T cells in the peripheral blood of celiac disease patients.
abstract: 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.
authors.affiliation: Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, 0027 Oslo, Norway. melinda.raki@medisin.uio.no
authors.forename: Melinda
authors.initials: M
authors.lastname: Ráki
authors.forename: Lars-Egil
authors.initials: LE
authors.lastname: Fallang
authors.forename: Margit
authors.initials: M
authors.lastname: Brottveit
authors.forename: Elin
authors.initials: E
authors.lastname: Bergseng
authors.forename: Hanne
authors.initials: H
authors.lastname: Quarsten
authors.forename: Knut E A
authors.initials: KE
authors.lastname: Lundin
authors.forename: Ludvig M
authors.initials: LM
authors.lastname: Sollid
mesh_terms: 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*
chemical_list: D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D005983:Glutens; D007371:Interferon-gamma