Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 110, Issue 32, Pages 13073-13078Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1311861110
Keywords
autoimmunity; mucosal immunity
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Funding
- National Institutes of Health (NIH) T32 Gastroenterology Training Grant
- American Cancer Society
- NIH [DK063158, AI057229-07, AI090019]
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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(+) alpha beta and gamma delta 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(+) alpha beta and gamma delta 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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