Dietary gluten triggers concomitant activation of CD4⁺ and CD8⁺ αβ T cells and γδ T cells in celiac disease
2013
Han, Arnold | Newell, Evan W. | Glanville, Jacob | Fernandez-Becker, Nielsen | Khosla, Chaitan | Chien, Yueh-Hsiu | Davis, Mark M.
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.
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