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Tetramer Visualization of Gut-Homing Gluten-Specific T Cells in the Peripheral Blood of Celiac Disease Patients
Melinda Ráki, Lars-Egil Fallang, Margit Brottveit, Elin Bergseng, Hanne Quarsten, Knut E. A. Lundin and Ludvig M. Sollid
Proceedings of the National Academy of Sciences of the United States of America
Vol. 104, No. 8 (Feb. 20, 2007), pp. 2831-2836
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/25426560
Page Count: 6
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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 β₇ 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.
Proceedings of the National Academy of Sciences of the United States of America © 2007 National Academy of Sciences