title: Dietary gluten triggers concomitant activation of CD4+ and CD8+ αβ T cells and γδ T cells in celiac disease.
abstract: Celiac disease is an intestinal autoimmune disease driven by dietary gluten and gluten-specific CD4(+) T-cell responses. In celiac patients on a gluten-free diet, exposure to gluten induces the appearance of gluten-specific CD4(+) T cells with gut-homing potential in the peripheral blood. Here we show that gluten exposure also induces the appearance of activated, gut-homing CD8(+) αβ and γδ T cells in the peripheral blood. Single-cell T-cell receptor sequence analysis indicates that both of these cell populations have highly focused T-cell receptor repertoires, indicating that their induction is antigen-driven. These results reveal a previously unappreciated role of antigen in the induction of CD8(+) αβ and γδ T cells in celiac disease and demonstrate a coordinated response by all three of the major types of T cells. More broadly, these responses may parallel adaptive immune responses to viral pathogens and other systemic autoimmune diseases.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Agency for Science, Technology and Research, Singapore 138648.
authors.forename: Arnold
authors.initials: A
authors.lastname: Han
authors.forename: Evan W
authors.initials: EW
authors.lastname: Newell
authors.forename: Jacob
authors.initials: J
authors.lastname: Glanville
authors.forename: Nielsen
authors.initials: N
authors.lastname: Fernandez-Becker
authors.forename: Chaitan
authors.initials: C
authors.lastname: Khosla
authors.forename: Yueh-Hsiu
authors.initials: YH
authors.lastname: Chien
authors.forename: Mark M
authors.initials: MM
authors.lastname: Davis
mesh_terms: D000284:Administration, Oral; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002446:Celiac Disease / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D004032:Diet; D005434:Flow Cytometry; D005983:Glutens / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D005983:Glutens
keywords: autoimmunity; mucosal immunity